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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

Research has demonstrated a NOAEL for parental and reproductive/developmental toxicity to be 50 mg/kg/day.

The impact on testes and sperm parameters is consistent with reproduction and repeat dose toxicity studies in rats and dogs, suggesting reproductive toxicty

This is consistent with furans (cyclic ether)

Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Up to 52 day dosing period, extending to day 4 lactation
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
Research working closely in line with OECD 415
Testing performed on major metabolite tetrahydrofurfuryl alcohol which is considered a suitable substitute for the ether.
Reason / purpose for cross-reference:
read-across: supporting information
Reason / purpose for cross-reference:
read-across: supporting information
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
Principles of method if other than guideline:
Rats were given tetrahydrofurfuryl alcohol (THFA) by gavage.
Males were dosed for 47 days, beginning 14 days before mating, and females were dosed for 42–52 days beginning 14 days before mating to day 4 of lactation
throughout the mating and gestation period
GLP compliance:
not specified
Limit test:
no
Justification for study design:
Follows accepted scientific principles
Specific details on test material used for the study:
99.5% purity
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
21.9–22.4 C,
Relative humidity of 49–57%,
12-h light/dark cycle
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on exposure:
Twelve male and female rats per group were given tetrahydrofurfuryl alcohol (THFA) by gavage at 0, 15, 50, 150 or 500 mg/kg/day. Males were
dosed for 47 days, beginning 14 days before mating, and females were dosed for 42–52 days beginning 14 days before mating to day 4 of lactation
throughout the mating and gestation period
Details on mating procedure:
After 14 days pre-,ating exposure, male and female rats (1:1) were placed in seperate cages
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
The concentrations in the formulations were confirmed to be 97.7–103.0% of nominal (gas chromatography).
Duration of treatment / exposure:
14 days prior to mating (males and females) and up to 4 days after birth (females)
Frequency of treatment:
Daily
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Vehicle only
Dose / conc.:
15 mg/kg bw/day (nominal)
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
150 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
No. of animals per sex per dose:
12 males and 12 females
Control animals:
yes, concurrent vehicle
Positive control:
No
Parental animals: Observations and examinations:
All animals were observed for clinical signs at least twice a day.
The body weight was recorded at least once a week
Oestrous cyclicity (parental animals):
Yes
Sperm parameters (parental animals):
Yes
Litter observations:
Yes
Postmortem examinations (parental animals):
Gross necropsy and more detailed pathology on reproductive organs
Postmortem examinations (offspring):
Viabilty, weight and gross necropsy
Reproductive indices:
Yes
Offspring viability indices:
Yes
Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Reduced activity in higher dose groups
Mortality:
mortality observed, non-treatment-related
Description (incidence):
One male died on Day 15 in a mid group. Not considered to be treatment related.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Reduced bodyweight gain at 500 mg/kg/day
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Reduced food consumptionin higher treatment levels
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
effects observed, treatment-related
Description (incidence and severity):
Reduced activity in higher groups
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Significant increases in the incidence of seminiferous tubular atrophy and hyperplasia of interstitial cells in the testes, and cell debris and decreased sperm at 500 mg/kg/day
Histopathological findings: neoplastic:
no effects observed
Other effects:
no effects observed
Reproductive function: oestrous cycle:
effects observed, treatment-related
Description (incidence and severity):
Oestrous cycle at 500 mg/kg prolonged
Reproductive function: sperm measures:
effects observed, treatment-related
Description (incidence and severity):
Reduced sperm parameters at 500 mg/kg/day
Reproductive performance:
effects observed, treatment-related
Description (incidence and severity):
No young from highest doese goup and reduced at 150 mg/kg/day
Dose descriptor:
NOAEL
Effect level:
ca. 50 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
organ weights and organ / body weight ratios
gross pathology
reproductive function (sperm measures)
reproductive performance
Critical effects observed:
yes
Lowest effective dose / conc.:
150 mg/kg bw/day (nominal)
System:
male reproductive system
Organ:
kidney
spleen
testes
Treatment related:
yes
Dose response relationship:
yes
Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Description (incidence and severity):
Live pups survived until termination
Body weight and weight changes:
no effects observed
Gross pathological findings:
no effects observed
Remarks on result:
not determinable due to absence of adverse toxic effects
Critical effects observed:
no
Reproductive effects observed:
yes
Lowest effective dose / conc.:
150 mg/kg bw/day (nominal)
Treatment related:
yes
Relation to other toxic effects:
reproductive effects in the absence of other toxic effects
Dose response relationship:
yes
Relevant for humans:
not specified
Conclusions:
The research demonstrated a NOAEL for parental and reproductive/developmental toxicity to be 50 mg/kg/day.
The impact on testes and sperm parameters is consistent with other repeat dose toxicity studies in rats and dogs, suggesting reproductive toxicty
This result is consistent with furan (cyclic ether)
Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Justification for classification or non-classification

Additional information