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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Cross-reference
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
two-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Adult breeder male and female Sprague-Dawley rats were were randomly assigned to one of three groups and fed one of
three semipurifed diets. Animals were allowed to breed and the offspring were weaned to the same diet as their dams. At
approximately 90 days of age, offspring from different parents within a diet group were mated to produce the F2 generation.
Offspring from both F1 and F2 generations were fed their respective diets throughout their entire lives.
Rats were fed AIN-G93 diets made with either casein protein (CAS), soy protein isolate (SPI), or whey protein hydrolysate (WPH) and bred. The birth weight, weight gains, body length, anogenital distance, and age of puberty (vaginal opening or preputial gland separation) of the F1 generation were measured. The F2 rats were euthanized and their organ weight was measured.
The breeding success (percent of males and females that produced offspring after mating) of the F1 generation, litter size, and percent of female offspring were investigated for three breeding sessions (at ages 90, 180, and 270 days).
GLP compliance:
not specified
Remarks:
published study
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on exposure:
All diets were made according to the AIN-93G diet formula (Reeves, Nielsen, and Fahey, 1993), except that corn oil replaced soy oil and the protein source was either CAS,WPH, or SPI. Amino acids were added to each diet to equalize the essential amino acids among diets.
Frequency of treatment:
The tested substance was incorporated to the diet and thus fed daili.
Details on study schedule:
At approximately 90 days of age, offspring from different parents within a diet group were mated to produce the F2 generation.
Dose / conc.:
200 000 mg/kg diet
Control animals:
yes, plain diet
Postmortem examinations (offspring):
body weights when examined in a separate set of rats at approximately age 55 days
Statistics:
Diet group was modeled as a between animals effect and day as a within animal effect. Organ weight and testosterone metabolism data were analyzed by one-way analysis of variance followed by Bonferroni post hoc analysis as described previously (Fisher and van Belle 1993).
Statistical signi cance was set at p < .05, and all p values are not adjusted for multiple comparisons.
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Endocrine findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
no effects observed
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Other effects:
no effects observed
Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed
Key result
Dose descriptor:
NOAEL
Effect level:
> 200 000 mg/kg diet
Sex:
male/female
Basis for effect level:
reproductive performance
Remarks on result:
not determinable due to absence of adverse toxic effects
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Slightly smaller offspring were observed in the WPH group.
Body weights of male rats fed SPI and WPH were similar to each other; and were slightly less than that of CAS-fed rats. Body weights started to diverge from those of CAS-fed pups prior to weaning; and became significantly lower than CAS-fed rats at age 7 weeks (p < .05). After age 7 weeks, body weight gains of SPI- and WPH-fed rats were approximately equal or slightly greater than CAS-fed rats, and by age 18 weeks all groups were statistically the same for body weights. Similar effects were observed in female rats, except that SPI-fed females did not begin to diverge from CAS-fed rats until 7 weeks, and by 9 weeks of age, the body weights of SPI- and WPH-fed rats did not differ significantly, but were less than (p < .05) CAS-fed rats. Thereafter, the body weight gains were approximately equal.
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
effects observed, treatment-related
Description (incidence and severity):
Male offspring fed CAS or SPI did not differ on the mean age of puberty (preputial gland separation), but WPH-fed offspring had puberty 2.0 days later ( p <.05) than CAS controls.
The mean age of puberty in female offspring (age of vaginal opening) was 2.0 days earlier ( p < .05) in the SPI-fed rats than the CAS group and the 1.3 days later ( p < .05) in the WPH group than the CAS group. The effects of diet on puberty were not affected by correction for gestational age.
Organ weight findings including organ / body weight ratios:
no effects observed
Other effects:
no effects observed
Behaviour (functional findings):
not specified
Developmental immunotoxicity:
not specified
WHP-fed male rats had delayed puberty (1.3 days) compared with CAS-fed rats as measured by preputial gland separation.
The breeding success of F1 rats and male/female ratios were not affected by diet.
Key result
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
> 200 000 mg/kg diet
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Key result
Dose descriptor:
NOAEL
Generation:
F2
Effect level:
> 200 000 mg/kg diet
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Reproductive effects observed:
no
Conclusions:
Rats fed either CAS, SPI, or WPH did not differ in breeding success rate and body size of offspring (birth weight and length).
Executive summary:

Not classified as toxic for reproduction

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Safety evaluation of fish protein hydrolysate supplementation in malnourished children
Author:
Knut Olav Nesse et al.
Year:
2014
Bibliographic source:
Regulatory Toxicology and Pharmacology 69 (2014) 1–6
Reference Type:
review article or handbook
Title:
Safety of protein hydrolysates, fractions thereof and bioactive peptides in human nutrition
Author:
G. Schaafsma
Year:
2009
Bibliographic source:
European Journal of Clinical Nutrition (2009), 1–8
Reference Type:
other: Review report
Title:
Review report for the active substance hydrolysed proteins
Author:
European Commission Directorate E – Safety of the food chain
Year:
2008
Bibliographic source:
SANCO/2615/08 – rev. 3

Materials and methods

Test animals

Species:
rat

Results and discussion

Applicant's summary and conclusion