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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route
Dose descriptor:
NOAEC
503 mg/m³
Additional information

Only one of the four studies available for this endpoint identified a quantitative NOAEL value which provided clear evidence of impaired fertility as a result of exposure to n-propyl bromide. This was a reliable study conducted to GLP using standard test methods and as such this value has been used as the key value for effects on fertility.

Whole-body inhalation exposure of Crl:CD(SD)IGS BR rats and the resulting offspring to vapor concentrations of 1-Bromopropane (100, 250, 500 and 750 ppm [F0 only]) for 6 hours per day, 7 days per week for a minimum of 70 days prior to mating and continuing until euthanasia produced no post-exposure clinical observations different from the control group animals exposed to filtered air. There were no mortalities related to exposure in the F0 generation. One F1 male in the 500 ppm group was euthanised in extremis during the second week of exposure. Body weight data (parental and pup) were reduced in the 500 (F0, F1 and F2) and 750 ppm (F0) groups. No macroscopic or microscopic pathology in brain tissue was observed. Complete lack of offspring was observed at exposures to 750 ppm, and a statistically decreased number of offspring compared to the control group was observed at exposures to 500 ppm (both generations). Non-statistically significant reductions in the number of offspring were observed in 250 ppm group for both generations. Fertility indices were statistically significantly reduced for the F0 500 ppm group. Reductions (not statistically significant) were observed in the 100, 250 and 500 ppm F1 groups. Extended estrous cycle lengths and an increase in the number of animals for which estrous cycle length could not be determined were observed in the 250 (F1), 500 (F0 and F1) and 750 (F0) ppm groups. The number of days between pairing and coitus were increased in the 500 and 750 ppm F0 groups. Reductions in organ weights were observed in the ovaries (500 and 750 ppm group F0 females), epididymides in the 250 (F0), 500 (F0 and F1) and 750 (F0) ppm group males, prostate (250, 500 and 750 ppm group F0 males), seminal vesicles (500 and 750 ppm group F0 males), pituitary in the 500 (F1) and 750 (F0) ppm group males and spleen in the F2 male and female weanlings. Organ weight differences from the control group values were also observed in the thymus (increase), liver (increase) and brain (decrease) in some groups. Generally, absolute values were different in treated animals compared to the control group values, but not when weights were expressed relative to body weights. Absolute brain weights were in the expected range for age, sex and strain, and no clinical or microscopic changes were correlated with the weight differences. No pathology was associated with the thymus weight increases, and increased lipid vacuolation and glycogen content of the liver was considered reversible, and not of biological significance. Spermatogenic endpoints were adversely affected in the 500 (F0 and F1) and 750 (F0) ppm group males. Microscopic findings were observed in the ovaries in the 500 (F0 and F1) and 750 (F0) ppm group females.


Short description of key information:
All toxicity to reproduction studies performed on n-propyl bromide were conducted using the inhalation route of exposure as due to the physicochemical properties of the substance this is the most likely route of exposure.
Five studies were available for this endpoint:
Stump. D.G. (2001a): NOAEL: 100 ppm (equal to a NOAEC of 503 mg/m3)
Stump. D.G. (2001b): No definitive conclusion possible
Hoffman. G.M. (2001): Study terminated early due to insufficient fertility.
Ichihara. G., et. al. (1999): No quantitative value established. Study concluded that the substance is a potential reproductive toxicant to men.
Garner C.E., et al. (2007): No quantitative value established. Activation of 1-bromopropane via CYP2E1 may contribute to the male reproductive toxicity.

Effects on developmental toxicity

Description of key information
All toxicity to reproduction studies performed on n-propyl bromide were conducted using the inhalation route of exposure as due to the physicochemical properties of the substance this is the most likely route of exposure.
Two studies were available for this endpoint:
Rodwell. D.E (2001) (full study): NOEL: maternal toxicity and fetal toxicity: 100 ppm; teratogenicity: 996 ppm
Rodwell. D.E (1999) (range finding study): NOEL: maternal toxicity: 100 ppm
Additional information

Neither of the available studies for this endpoint identified a quantitative NOAEL value. However, the studies do provide suspicion of developmental toxicity as a result of exposure to 1-bromopropane. The lowest NOEL value established for the developmental toxicity and teratogenicity of 1-bromopropane is 100 ppm (equal to 503 mg/m³).

Justification for classification or non-classification

Based upon the above results, according to section 4.2.3 of Directive 67/548/EEC, the substance does meet the criteria for classification as a substance that should be regarded as if it would impair fertility in humans (Repr. Cat. 2; R60). In addition, the substance also meets the criteria for classification as a substance that should be regarded as causing concern for humans owing to possible developmental toxic effects (Repr. Cat. 3; R63).

As such, n-propyl bromide is officially classified as Repr. Cat. 2; R60 and Repr. Cat. 3; R63 on Annex I of Directive 67/548/EEC and as a Reproductive toxicant Category 1B on Annex VI of the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.