Test and Results:pve Irrit atiog Protocol: New Zealand White Rabbits, 9 female, 2 to 3 kg; a topical anesthetic instilled in all rabbit eyes approximately 2 min prior to treatment; 0.1 mL into conjunctival sac, contralateral eye as untreated control; washed eyes flushed with lukewarm water for 1 min, 20 to 30 sec after treatment; Draize scoring technique'. Draize Scores: Unwashed (6 rabbit mean) 1 d 0 . 0 , 2 d 0 . 0 , 3 d 0 . 0 , 4 d 0 . 0 , 7 d 0.0; Washed (3 rabbit mean) 1 d 0.0, 2 d 0 . 0 , 3 d 0 . 0 , 4 d 0.0, 7 d 0 , Q Results: Nonirritating skin Irri tation Protocol: New Zealand white Rabbits, 6 female, 2 to 3 kg; apply 0.5 mL to intact and abraded skin; cover with gauze pad, dental dam, and elastic tape; patches removed at 24 h; wipe clean and evaluate at 1 h, 1, 2, 3, and 7 days using Draize technique'. -Primary dermal irritation index = 1.29, slightly irritating. ennal Sensitizatio Protocol: Ten Hartley, male, albino guinea pigs, 6 t o 8 Eeeks of age, N=10;'0.1 mL topically applied four times over a 10-day period. Following a two-week induction period, the animals were challenged with 0.1 mL of the test material on the clipped flank. Site scored for edema and erythema at 24 and 40 h; Draize technique. Results: 101 of tho animals showed a sensitization response; weak sensitizing potential. 'DRAIZE, J.H. (1959) Dermal Toxicitv. ADD raisal of the Safetv of Chemicals in Food, Druas, and Cosmetics. Assoc. of Food and Drug Officials of the U.S., Austin, TX, 49-51.
Quadricyclane CASR 278-06-8 Compound Tested: Oral -Neat and as 70/30 mixture with kerosene Dermal -Neat Dose Preparation: Test and Results:Oral Lethalitv Protocol: Male Fischer 344 rats were fasted for approximately 16 hours prior t o administration of the oral dose. Each rat was weighed prior to dosing and the test compound was administered on a g/kg basis. Five rats received a dose of 3.5 g quadricyclane/kg; five rats received a dose of 1.7 g/kg of a quadricyclane/kerosene mixture (70% to 30%); five rats received a dose of 4.3 g kerosenelkg; and five rats received 5 g salinefkg to serve as controls. Surviving animals were held 14-days posttreatment. Results: All were prostrate immediately following dosing and remained so until death. 1.1 g/kg mixture resulted in prostration in all rats through 24 hours posttreatment; returned to normal appearance and activity by 4 8 hours and survived the 14-day posttreatment period. Tissues examined from animals following death were equivocal. Tissues from animals that survived the 14-day posttreatment period appeared normal. These data indicate an LD, between 1.2 and 3.5 g/kg.Dermal Lethality Protocol: Five male albino New Zealand White rabbits were used. The saddle area was clipped and the neat compound was applied at the EPA limit level of 2 g/kg body weight. The area was covered with gauze bandage and dental dam. The entire midsection was then wrapped in elastoplast tape. After 24 hours, the covering was removed and excess compound was wiped from the rabbit. The rabbits were observed 14-days posttreatment. Results: One of the five rabbits died of accidental injury during the treatment period. The four remaining rabbits survived the 14-day posttreatment period and appeared normal upon gross examination.3.5 g/kg neat compound resulted in total mortality within 24 hours.
Currently, N-methyl-N'-nitroguanidine (MNG) is being considered by the U.S. Air Force Armament Laboratory for use in explosive formulations. A mammalian toxicity profile has been performed which includes the analysis of chemical impurities and an assessment of the potential for the metabolism of MNG to 1-methyl-3-nitro-1-nitrosoguanidine (MNNG). Potential in situ gastric conversion of MNG to MNNG is a toxicological concern because MNNG is both mutagenic and carcinogenic. The compound was also evaluated in several bioassays to assess its potential genotoxic activity. The acute oral toxicity was determined in male and female Fischer 344 rats administered a single dose of MNG in corn oil. The maximum suspension of MNG that could be delivered, 1 mg MNG/kg body weight, produced no signs of toxic stress during the 14-day observation period. The primary eye and skin irritation potential of MNG was determined in female New Zealand white rabbits using the Draize technique. MNG produced no irritation to intact skin but did produce mild conjunctival irritation. The response of a single guinea pig to the dermal sensitization evaluation indicated that MNG is a weak sensitizer. The results of three genetic tests indicated that MNG does not interact with genetic material. Gastric contents and feces from treated animals showed no evidence of conversion of MNG to MNNG.
Liquid propellant XM46 is being considered as a replacement for solid propellants, both as part of a regenerative injection gun system and as a working fluid in an electrothermal gun system. The XM46 formulation contains hydroxylammonium nitrate, triethanolammonium nitrate, and water. Male and female Sprague-Dawley rats received XM46 in drinking water containing 2.0, 1.0, 0.2, or 0.0 g XM46/liter throughout a 90-day study. Mating occurred following 14 days of treatment. One-half the male rats per group were necropsied after 28 days of treatment; the remaining males and all dams were necropsied following 90 days of treatment. No mortality occurred in any of the parental animals during the study. The study did not demonstrate any adverse effects on reproduction or litter parameters. Hemolytic anemia and methemoglobinemia were common in both sexes of rats. Splenomegaly was found in both sexes; in male rats as early as 28 days. Exposures via drinking water containing XM46 for 90 days did not result in any decrease in reproductive performance in male or female rats, but it did result in clinical signs of hemolytic anemia at doses as low as 17 mg/kg/day.
Test and Results:Fve Irritation Protocol: New Zealand White Rabbits; 9 female; 2 to 3 kg; a topical anesthetic instilled in all rabbit eyes approximately 2 min prior to treatment; 0.1 mL into conjunctival sac, contralateral eye as untreated control; washed eyes flushed with lukewarm water for 1 min, 20 to 30 sec after treatment; Draize scoring technique'. Draize Scores: Unwashed (6 rabbit mean) Id 0.0, Id 0.0, 3d 0.0, 4d 0.0, ld 0.0 Washed (3 rabbit mean) Id 0.0, 2d 0.0, 3d 0.0, 4d 0.0, ld 0.0 Results: Nonirritating. Skin Irri tation Protocol: New Zealand White Rabbits, 6 female, 2 to 3 kg; apply 0 . 5 mL to intact and abraded skin; cover with gauze pad, dental dam, and elastic tape; remove wraps after 24 hours; wipe clean and evaluate at 1 h, 1, 2, 3, and 1 day8 using Draize technique'. Primary dermal irritation index = 0.04, nonirritating. Dermal Sensitizatioq Protocol: Twenty Hartley male albino guinea pigs, 6 to 8 weeks of age; Modified Landsteiner Test'; 7 id injections (0.1 mL of 0.01% in peanut oil) at lumbro-sacral area over a 15-day period. Following a three-week induction period, the animals were challenged with 0.05 mL of the test material in scapular area. Reaction scored at 24 and 48 hours for edema and erythema. Potential based on number of animals showing sensitization response. Results: 30% of the animals demonstrated a sensitization response; moderate sensitizing potential. 'DRAIZE, J. H. (1959) permal Toxicitv, A~~r a i s a l of the Safetv of Chemicals in Food. Druas. and Cosmetics, Assoc. of Food and Drug Officials of the U . S . , Austin, TX, 49-51. 'LANDSTEINER, K., and JACOBS, J. Studies on the sensitization of animals with simple chemical compounds. J . EXD. Med. 62:643-656. (1953) 706
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