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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on test guideline (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
IUCLID4 Test substance: other TS
TS-Freetext:
Mesamoll = C10-21 Alkane sulfonic acids phenyl esters
Purity: 100,1 %

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: administered in diet
Details on mating procedure:
Premating period of F0 rats= 10 weeks
mating period F0 rats = up to 21 days
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Exposure period: 10 weeks pretreatment
up to 3 weeks mating
3 weeks gestation
4 nursing
Premating exposure period (males): 10 weeks
Premating exposure period (females): 10 weeks
Duration of test: 17 - 20 weeks
Frequency of treatment:
permanent
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 600, 3000 and 15000 ppm in diet
Basis:

No. of animals per sex per dose:
25/sex/dose
Control animals:
yes, concurrent no treatment

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Key result
Dose descriptor:
NOAEL
Effect level:
600 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Increase in altered follicular colloid in the thyroids

Results: P1 (second parental generation)

Effect levels (P1)

Remarks on result:
other: see 'Remark'
Remarks:
One-generation study in Wistar rats (Administration in the diet)

Results: F1 generation

Effect levels (F1)

Remarks on result:
other: see 'Remarks'
Remarks:
One-generation study in Wistar rats (Administration in the diet)

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Result: above 600 ppm in the diet: reductions of food consumption and body weight  gain in females during gestation and lactation (high dose), retardation  of fetal weight and development (mid and high dose)
No other effects

Applicant's summary and conclusion

Executive summary:

In an one-generation study Mesamoll was administered to groups of 25 male and 25 female rats each at concentrations of 0 (control), 600, 3000, and 15000 ppm in their diet.

Parenteral F0 animals were pretreated over a period of about 10 weeks and allowed to mate over a period of up to three weeks. F1 offspring were nursed up to an age of four weeks. Some of them were selected for further treatment up to necropsy when developmental milestones has occured.

Clinical signs, body weight, food intake, mating performance, fertiliy, duration of pregnancy, estrus cycling and sperm parameters were examined in F0 rats. Litter size, percentage of male born and pup weight at birth as well as viability, rearing, lactation and body weight gain were studied in F1 offspring. developmental milestones were examined in F1 weanlings. necropsies were done in all rats. Implantation sites were recorded in F0 females. Selected organs were weighed (F0 and F1) and histopatological evaluations were performed on some organs of F0 rats.

Mortality and clinical appearance in F0 and post weaned F1 animals were unchanged at levels of up to 15000 ppm.

There was no adverse effect on body weight development in F0 males up to 15000 ppm. 15000 ppm F0 females exhibited retarded body weights mainly during gestation and lactation. Significant body weight reduction was also noted at necropsy of 15000 ppm post weaned F1 males.

The increase in food intake of 3000 and 15000 ppm F0 females is not considered as adverse.

The reproduction parameters insemination index, mating performance, fertility index, gestation index, duration of pregnancy, life birth index, birth weights, percentages of males born, total number of pups born, prenatal loss, mean litter size at birth as well as viability and lactation index were not affected at levels of up to 15000 ppm.

The body weight development of F1 pups was retarded at 3000 and 15000 ppm resulting in pup organ weight changes at 15000 ppm.

No test substance-related clinical or gross pathological findings were observed in F1 offspring up to 15000 ppm. The skeletal development of the offspring was unaffected.

No adverse effect was seen in sperm parameters at 15000 ppm.

The occurring of developmental milestones was unaffected in 600 ppm F1 rats. From 3000 ppm onwards delayed balano-preputial separation and at 15000 ppm delayed vaginal opening were noted as a consequence of retarded body weight development during lactation and/or post weaning period.

F0 females exhibited no treatment effects on estrus cycling up to 15000 ppm.

The increase in altered follicular colloid in the thyroids from 3000 ppm onwards in F0 animals (males 15/25, 16/25, 22/25 and 23/25 at 0, 300, 600 and 3000 ppm respectively; females 1/25, 4/25, 4/25 and 5/25, respectively) and the slightly higher frequency of males exhibited follicular cell hypertrophy at 15000 ppm (1/25, 1/25, 1/25, 7/25, respectively) are not interpreted as a specific effect on the hormone system because these findings are noted frequently especially in male rats and are considered as unspecific expression of adaptive physiological changes and the observations in females are not dose dependent. In addition, no effects on thyroid histopathology was reported in the sub-chronic toxicity study .

Elevated kidney weights in F0 rats partly from 3000 ppm onwards indicate unspecific changes in kidney function, because morphological correlates are missing. Since indications of liver damage are lacking the increase of liver weights found in females at 3000 ppm and above are interpreted to be a result of changed liver function.

Gross pathology and histopathology in remaining organs revealed no treatment-related lesions.

Thus, the dietary concentration of 600 ppm is established as NOAEL for the parent animals and reproduction parameters.