Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Peer reviewed source.

Data source

Reference
Reference Type:
publication
Title:
Lack of effect on rat testicular organogenesis after in utero exposure to 3-monochloropropane-1,2-diol (3-MCPD)
Author:
El Ramy R, Elhkim MO, Poul M, Forest MG, Leduque P, and Le Magueresse-Battistoni B
Year:
2006
Bibliographic source:
Reproductive Toxicology 22 (2006) 485-492

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Not given.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
3-chloropropane-1,2-diol
EC Number:
202-492-4
EC Name:
3-chloropropane-1,2-diol
Cas Number:
96-24-2
IUPAC Name:
3-chloropropane-1,2-diol
Constituent 2
Reference substance name:
3-Chloro-1,2-propanediol
IUPAC Name:
3-Chloro-1,2-propanediol

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Details on mating procedure:
The morning after mating was designated as day 0.5 of gestation and was confirmed by the presence of sperm in vaginal saline washes.
Duration of treatment / exposure:
Testicular gene expression: From gestational day 11.5 through day 18.5
Apoptosis and cell proliferation detection: From gestational day 11.5 through day 18.5
3-MCPD and beta-chlorolactic acid levels in dam plasma and in whole fetuses: Day 14.5 postcoitum
Frequency of treatment:
Daily.
Duration of test:
Testicular gene expression: Pregnant rats were sacrificed on day 19.5 postcoitum.
Apoptosis and cell proliferation detection: Animals were allowed to deliver and assays were performed on 3 to 5 days-old testes.
3-MCPD and beta-chlorolactic acid levels in dam plasma and in whole fetuses: Animals from each group were sacrificed at 30 min, 1, 2, 3, 5 or 8 h after treatment.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 5, 10 or 25 mg/kg bw (Testicular gene expression)
Basis:

Remarks:
Doses / Concentrations:
0 or 25 mg/kg bw (Apoptosis and cell proliferation detection)
Basis:

Remarks:
Doses / Concentrations:
0 or 25 mg/kg bw (3-MCPD and beta-chlorolactic acid levels)
Basis:

No. of animals per sex per dose:
Testicular gene expression: 5 - 6 pregnant female rats per dose.
Apoptosis and cell proliferation detection: 5 pregnant female rats per dose.
3-MCPD and beta-chlorolactic acid levels in dam plasma and in whole fetuses: 21 pregnant rats (in groups of 3 animals each).

Examinations

Maternal examinations:
Yes by cage side.
Ovaries and uterine content:
Yes after termination.
Fetal examinations:
Testicular gene expression: For RNA analysis, testes from male fetuses of the same litter were pooled. Additional testes were collected at 19.5 days postcoitum for histology. Testes from a further group of male fetuses were used for the measurement of testosterone levels. Sex ratio and body weights of fetuses were also obtained.

Apoptosis and cell proliferation detection assays were performed on 3 to 5 day-old testes.

3-MCPD and beta-chlorolactic acid levels: The placental/fetal units were removed from the uterus and the fetuses were separated from the placenta, sampled and weighed. Fetal tissues were analyzed for 3-MCPD and beta-chlorolactic acid.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Effect levels (maternal animals)

Dose descriptor:
LOAEL
Effect level:
> 5 - <= 10 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 25 mg/kg bw/day
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEL
Effect level:
> 25 mg/kg bw/day
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The results show a decrease in the mean body weight gain of pregnant rats treated at 10 and 25 mg/kg BW. Fetal testes exposed at doses up to 25 mg/kg bw/day exhibited normal histology and produced testosterone at levels that were similar to controls. In addition, the substance did not alter gene expression in the fetal testes at doses up to 25 mg/kg bw/day. This lack of effect occurred under conditions where the substance and beta-chlorolactic acid (the main metabolite of the substance) were found to readily cross the placental barrier and diffuse throughout the fetal tissues. Under the conditions of this study, the substance has minimal effect on rat testicular organogenesis.