scholarly journals Toxicology Studies on Lewisite and Sulfur Mustard Agents: Two-Generation Reproduction Study of Lewisite in Rats Final Report

1989 ◽  
Author(s):  
L. B. Sasser ◽  
J. A. Cushing ◽  
D. R. Kalkwarf ◽  
P. W. Mellick ◽  
R. L. Buschbom
Keyword(s):  
Sulfur Mustard ◽  
Final Report ◽  
Reproduction Study

scholarly journals Final Report on the Safety Assessment of Toluene-2,5-Diamine, Toluene-2,5-Diamine Sulfate, and Toluene-3,4-Diamine

1992 ◽  
Vol 11 (4) ◽  
pp. 423-445 ◽  
Keyword(s):  
Laboratory Animals ◽  
Final Report ◽  
Hair Dyes ◽  
Pregnant Rats ◽  
Hair Dye ◽  
Dermal Irritation ◽  
Cosmetic Ingredients ◽  
Reproduction Study ◽  
Conjunctival Inflammation ◽  
Rats And Mice

The diaminotoluenes 2,5-TD, 2,5-TDS, and 3,4-TD are used as colorants in permanent hair dyes and tints. 2,5-TD is used at concentrations up to 1 % and 2,5-TDS is used up to 5%. The major routes of excretion after cutaneous absorption by rats were through the urine and feces. The oral LD50 of 2,5-TDS in rats was 98 mg/kg. There was no evidence of percutaneous toxicity to rabbits when 6% 2,5-TDS was applied to intact or abraded skin. In a two-year study, no toxicity was reported in rats receiving biweekly cutaneous applications of formulations containing 3% or 4% 2,5-TD. Mice were also unaffected by 3% 2,5-TDS in an 18-month study, or by 3% 2,5-TD in a two-year study. Rabbits had a slight dermal irritation response after exposure to 2.5% 2,5-TDS, but no irritation occurred in guinea pigs after exposure to 10% solutions of 2,5-TDS or 3,4-TD. 2,5-TD (2.5%) caused mild, transitory conjunctival inflammation in rabbits. The results of sensitization tests of 2,5-TD, 2,5-TDS, and 3,4-TD indicated that each of these diaminotoluenes were sensitizers to laboratory animals and humans. 2,5-TDS was toxic to pregnant rats and their embryos at oral doses of 80 mg/kg/day. Doses between 10 and 50 mg/kg/day did not cause congenital or maternal abnormalities. o-Toluenediamine, a mixture of 2,3-TD and 3,4-TD (40:60), was not teratogenic when administered orally to rats or rabbits. Cutaneous exposure to hair dye formulations containing 3% 2,5-TDS caused a statistically significant increase in fetal skeletal anomalies in rats. Rats treated with 6% 2,5-TDS did not have this adverse response. In a two-generation reproduction study, mice receiving dermal applications of hair-dye formulations containing either 3% or 6% 2,5-TDS had no signs of pharmacotoxicity, teratogenicity, or reproductive abnormalities. The results cited from various mutagenicity assays of 2,5-TD, 2,5-TDS, and 3,4-TD varied in accordance with the assay system and protocols used. 2,5-TD and 2,5-TDS were noncarci-nogenic to rats and mice in both oral and dermal exposure studies. On the basis of the animal and clinical data presented in this report, and the required labeling, it is concluded that Toluene-2,5-Diamine Sulfate and Toluene-3,4-Diamine are safe as cosmetic ingredients in the present practices of use.

Japanese Perspectives on the Reproductive and Developmental Toxicity Evaluation of Pharmaceuticals

1990 ◽  
Vol 9 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Takashi Tanimura
Keyword(s):  
International Organizations ◽  
Developmental Toxicity ◽  
Human Reproduction ◽  
Current Status ◽  
Final Report ◽  
Toxicity Evaluation ◽  
Scientific Discussion ◽  
Reproduction Study ◽  
Behavioral Teratology ◽  
Japanese Guidelines

The current Japanese guidelines for reproductive and developmental toxicity studies of drugs stress the need for examination of the effects of drugs on the behavior and fertility of the offspring. In 1986, the Ministry of Health and Welfare initiated a review of all current toxicity test guidelines, one of the objectives of the review being to increase the international harmonization of such guidelines. The final report of the Reproduction Study Subgroup was officially released on September 11, 1989. A summary of the conclusions of the study subgroup follows: To attain international conformity of guidelines requires scientific discussion among international organizations, but an early solution will be difficult. A more practical way is to accept studies performed in conformity with other guidelines if the applicant submits a document demonstrating that the same degree of safety for human reproduction and development required by the Japanese guidelines can be judged from the characteristics and clinical indications of the drug., Positive discussion is also necessary with other countries to agree on conditions under which studies performed according to the Japanese guidelines will be acceptable to such countries. In addition, the current status of behavioral teratology tests in Japan surveyed by the Behavioral Teratology Meeting, Japanese Teratology Society is presented.

scholarly journals Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity of Sulfur Mustard (HD) In Rats Final Report

1989 ◽  
Author(s):  
L. B. Sasser ◽  
R. A. Miller ◽  
Kalkwarf, D, R. ◽  
R. L. Buschbom ◽  
J. A. Cushing
Keyword(s):  
Sulfur Mustard ◽  
Final Report ◽  
Subchronic Toxicity

scholarly journals Teratology studies of lewisite and sulfur mustard agents: Effects of lewisite in rats and rabbits: Final report

1987 ◽  
Author(s):  
P L Hackett ◽  
L B Sasser ◽  
R L Rommereim ◽  
J A Cushing ◽  
R L Buschbom ◽  
...  
Keyword(s):  
Sulfur Mustard ◽  
Final Report

scholarly journals Toxicology Studies on Lewisite and Sulfur Mustard Agents: Subchronic Toxicity Study of Lewisite in Rats Final Report

1989 ◽  
Author(s):  
L. B. Sasser ◽  
J. A. Cushing ◽  
D. R. Kalkwarf ◽  
P. W. Mellick ◽  
R. L. Buschbom
Keyword(s):  
Sulfur Mustard ◽  
Toxicity Study ◽  
Final Report ◽  
Subchronic Toxicity

Two-generation reproduction study of sulfur mustard in rats

1996 ◽  
Vol 10 (4) ◽  
pp. 311-319 ◽  
Author(s):  
Lyle B. Sasser ◽  
Jackie A. Cushing ◽  
Jack C. Dacre
Keyword(s):  
Sulfur Mustard ◽  
Reproduction Study

scholarly journals Teratology studies of lewisite and sulfur mustard agents: Effects of lewisite in rats and rabbits: Final report: Part 2, Appendices

1987 ◽  
Author(s):  
P.L. Hackett ◽  
L.B. Sasser ◽  
R.L. Rommereim ◽  
J.A. Cushing ◽  
R.L. Buschbom ◽  
...  
Keyword(s):  
Sulfur Mustard ◽  
Final Report
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