Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Toxic effect type:
concentration-driven

Effects on fertility

Description of key information

OECD 416 guideline study in rats, NOAEL 50 mg/kg bw/day;

Link to relevant study records
Reference
Endpoint:
two-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
Version / remarks:
EPA/TSCA
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Housing: wire mesh cages
- Diet: Ralson Purina commercial laboratory feed, ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65 - 79
- Humidity (%): 17 - 76
- Photoperiod (hrs dark / hrs light): 12
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on mating procedure:
- M/F ratio per cage: 1/1
- Length of cohabitation: 7 nights, if female was still not pregnant, she was moved to another male for an additional 7 nights, and then to a third male if needed
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged individually
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Daily
Frequency of treatment:
F0: Treatment was started 10 weeks before mating. For males, dosing continued for 2 weeks after mating (total of 105 days). For females, dosing continued through lactation for a total of 127 treatment days.

F1: The F1 generation was treated similarly to the F0 generation, but were exposed beginning 11 weeks pre-mating.
Dose / conc.:
5 mg/kg bw/day (actual dose received)
Dose / conc.:
50 mg/kg bw/day (actual dose received)
Dose / conc.:
500 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
30
Control animals:
yes, concurrent vehicle
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: males - weekly, females - weekly before mating, days 0, 7, 14, and 20 of gestation, and days 0, 4, 14, and 21 of lactation

FOOD CONSUMPTION: weekly

Litter observations:
STANDARDISATION OF LITTERS
- F1 pups were selected for mating at weaning, at least one pup per litter was selected for the adult F1 generation

PARAMETERS EXAMINED
The following parameters were examined in F1 and F2 offspring:
- number and sex of pups on days 0, 4, 7, 14, and 21 of lactation,
- postnatal mortality
- presence of gross anomalies daily, weights on days 0, 4, 7, 14, and 21 of lactation

GROSS EXAMINATION OF DEAD PUPS:
yes
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All surviving animals 2 weeks after mating.
- Maternal animals: All surviving animals at weaning.

GROSS NECROPSY
- Gross necropsy consisted of examination for gross lesions

HISTOPATHOLOGY / ORGAN WEIGHTS
pituitary glands, testes and epididymides, prostate and seminal vesicles, vagina, uterus, ovaries, and gross lesions
Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at weaning.
- These animals were subjected to postmortem examinations similar to parental animals above.
Reproductive indices:
Mating index, pregnancy rate, fertility index
Offspring viability indices:
Pup survival
Clinical signs:
effects observed, treatment-related
Dermal irritation (if dermal study):
not examined
Mortality:
mortality observed, non-treatment-related
Description (incidence):
No mortality attributed to treatment was observed.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean body weights of high-dose-group (500 mg/kg bw/d) males were significantly and consistently reduced (12 = 0.01) in the F0 (since premating week); mean body weights of high-dose females were significantly decreased in the F0 generation since the 9th week of premating until the first week of lactation (p = 0.05); body weight reduction was significant on day 20 of gestation in both generations (p = 0.01)
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Description (incidence and severity):
No histopathological findings.
Histopathological findings: neoplastic:
no effects observed
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
effects observed, treatment-related
Description (incidence and severity):
Mating, pregnancy and fertility rates were not influenced.
Key result
Dose descriptor:
NOAEL
Remarks:
reproductive performance
Effect level:
>= 500 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: no effect of reproductive performance was observed
Key result
Dose descriptor:
NOEL
Remarks:
systemic toxicity
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
other: Litter size
Dose descriptor:
LOAEL
Effect level:
500 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
other: Litter size
Key result
Critical effects observed:
no
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):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Other effects:
effects observed, treatment-related
Description (incidence and severity):
OTHER FINDINGS (OFFSPRING)
In the high-dose-group, gestation length was significantly increased for the F2 litter interval (22.4 d compared to 22.0 in controls).
Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
not examined
Key result
Dose descriptor:
NOAEL
Remarks:
reproductive performance
Effect level:
>= 500 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Remarks on result:
other: no effect of reproductive performance was observed
Key result
Dose descriptor:
NOAEL
Remarks:
systemic toxicity
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: gestation length
Key result
Critical effects observed:
no
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
Litter size F1: significant decrease at 500 mg/kg bw/d (p = 0.05 and 0.01 respectively).
Pup viability index at birth F1: significant decrease at 50 and 500 mg/kg bd/d (p = 0.05); survival of pups at day 4 was significantly decreased at 500 mg/kg bw/d in the F1 litters.
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean pup weight F1 litters; significant reduction at 50 and 500 mg/kg bw/d at day 7 and only at 500 mg/kg bw/d at day 14 and 21 (p = 0.05), since the reduction in the 50 mg/kg bw/d group was only noted at day 7 and only in the F1 generation, this effect was not considered biologically significant
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Sexual maturation:
not examined
Anogenital distance (AGD):
not examined
Nipple retention in male pups:
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Key result
Dose descriptor:
NOEL
Remarks:
developmental toxicity
Generation:
F1
Effect level:
5 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
body weight and weight gain
Dose descriptor:
LOAEL
Generation:
F1
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
body weight and weight gain
Key result
Critical effects observed:
no
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
Litter size F2: significant decrease at 500 mg/kg bw/d (p = 0.05 and 0.01 respectively).
Pup viability index at birth F2: significant decrease at 500 mg/kg bw/d (p = 0.05), since effects at 50 mg/kg bw/d was only noted in a single generation, these effects were not considered biologically significant; survival of pups at day 4 was significantly decreased at 500 mg/kg bw/d in F2 litters; survival of pups at day 21 (related to day 4) was significantly decreased only in the F2 litter at 50 mg/kg bw/d (p = 0.05), since effects at 50 mg/kg bw/d was only noted in a single generation, these effects were not considered biologically significant
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean pup weight F2 litters: significant reduction at 500 mg/kg bw/d at day 14 and 21 (p = 0.05).
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Sexual maturation:
not examined
Anogenital distance (AGD):
not examined
Nipple retention in male pups:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Histopathological findings:
not specified
Behaviour (functional findings):
not examined
Developmental immunotoxicity:
not examined
Key result
Dose descriptor:
NOEL
Remarks:
developmental toxicity
Generation:
F2
Effect level:
50 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
viability
body weight and weight gain
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no

Table 1: Litter Size and Pup Survival Indices

Dose (mg/kg/day)

Litter size (mean)

Pup viability index at birth (%)

Pup survival days 0 - 4 (%)

Pup survival days 0 - 4 (%)1

Pup survival days 4 - 21 (%)

F1 litters

0

12.7

99.1

93.8

95.7

5

12.8

98.0

93.4

91.0

50

13.1

95.4

92.3

84.2

500

10.0

95.4

85.0

94.7

F2 litters

0

11.3

98.6

80.2

93.5

98.1

5

11.6

98.2

87.3

94.4

97.1

50

13.1

97.3

89.5

92.3

89.1

500

7.0

89.0

84.1

85.9

97.3

1Excludes data for litters in which all pups died during the Day 0 - 3 interval.

Table 2: Mean Pup Weights (g)

Dose (mg/kg/day)

Day 0

Day

4 - Precull

Day

4 - Postcull

Day

7

Day 14

Day

21

F1 litters

0

6.0

8.4

8.4

13.2

27.0

42.7

5

5.9

8.1

8.1

12.9

27.3

42.1

50

5.8

7.5

7.6

11.4

25.1

39.6

500

5.8

8.1

8.1

11.4

23.5

37.7

F2 litters

0

5.8

8.1

8.3

13.9

27.0

40.5

5

5.8

8.5

8.5

14.4

26.9

42.0

50

6.0

8.1

8.1

13.4

25.3

39.5

500

5.8

8.1

8.1

12.1

22.3

34.6

Conclusions:
The NOEL for the maternal and paternal generation was 50 mg/kg bw/day and for the offspring generations. No effects on fertility were observed.
Executive summary:

This study in accordance with OECD 416 and in compliance with GLP the effects of exposure to the test substance on reproduction were examined. Groups of 30 female and 30 male rats were exposed to concentrations of 0, 5, 50 and 500 mg/kg day of test substance by oral gavage beginning ten weeks before mating. Animals were then mated. The resulting generation was also exposed to the test substance and mated. Exposure continued through the mating period, and in females through the gestation and lactational periods. All animals were sacrificed and necropsied after exposure. Pups not used for mating were sacrificed at weaning. During the study, animals were observed for clinical signs, mortality, and body weight. Pups were examined for viability and body weight gain. Reproductive indices were also calculated. The NOAEL for parental toxicity was 50 mg/kg/day and the LOAEL was 500 mg/kg/day based on reduced weight gain and litter size in the high dose group. The NOAEL for offspring was 50 mg/kg/day based on reduced body weight gain and survival in the high and mid-dose groups. The LOAEL for offspring was 50 mg/kg/day. No effects on fertility were observed.

Effect on fertility: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
50 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Key study is two-generation reproductive study, reliable with restrictions.
Additional information

This study examined the effects of exposure to the test substance on reproduction. Groups of 30 female and 30 male rats were exposed to concentrations of 0, 5, 50 and 500 mg/kg day of test substance by oral gavage beginning ten weeks before mating. Animals were then mated. The resulting generation was also exposed to the test substance and mated. Exposure continued through the mating period, and in females through the gestation and lactational periods. All animals were sacrificed and necropsied after exposure. Pups not used for mating were sacrificed at weaning. During the study, animals were observed for clinical signs, mortality, and body weight. Pups were examined for viability and body weight gain. Reproductive indices were also calculated. The NOAEL for parental toxicity was 50 mg/kg/day and the LOAEL was 500 mg/kg/day based on reduced weight gain and litter size in the high dose group. The NOAEL for offspring was 50 mg/kg/day based on reduced body weight gain and survival in the high and mid-dose groups. The LOAEL for offspring was 500 mg/kg/day.

Effects on developmental toxicity

Description of key information

OECD 414 guideline study in rats, NOAEL 125 mg/kg bw/day

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Groups of 24 mated female rats were exposed to concentrations of 0, 125, 500, and 2000 mg/kg bw/day of test substance by oral gavage during days 6 - 15 of gestation. On day 20 of gestation, the animals were sacrificed and the uterine contents examined. Pups were removed by caesarean section and soft tissue and skeletal examinations performed.
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on mating procedure:
- M/F ratio per cage: 1/1
- Length of cohabitation: 7 nights, if female was still not pregnant, she was moved to another male for an additional 7 nights, and then to a third male if needed
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged individually
Duration of treatment / exposure:
Days 6 - 15 of gestation
Frequency of treatment:
Daily
Duration of test:
Section on 20th of gestation
Dose / conc.:
125 mg/kg bw/day (actual dose received)
Remarks:
Group 2, low dose
Dose / conc.:
500 mg/kg bw/day (actual dose received)
Remarks:
Group 3, mid dose
Dose / conc.:
2 000 mg/kg bw/day (actual dose received)
Remarks:
Group 4, high dose
No. of animals per sex per dose:
24 mated females rats/dose and control groups
Control animals:
yes, concurrent vehicle
Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 6, 10, 12, 15, and 20 of gestation

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: complete post-mortem examination

Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: number of live and dead fetuses, sex of fetuses
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
Statistics:
Nair, RS, Auletta, CS, Schroeder, RE, and Johannsen, FR (1990). Chronic toxicity, oncogenic potential, and reproductive toxicity of p-nitroaniline in rats. Fundam. Appl. Toxicol. 15, 607 - 621.
Indices:
Incidence of fetuses and litters with malformations and resorption sites
Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not examined
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean body weight gains were significantly decreased since the 10th day of gestation in the 2000 mg/kg bw/d group (p <= 0.01) and from the 12th to 15th day of gestation in the 500 mg/kg bw/d group; compensatory increases of weight gains occurred in the posttreatment period in these groups;
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Food consumption was significantly reduced during treatment (p ≤ 0.01) and significantly increased after treatment in the 500 mg/kg bw/d (p ≤ 0.005) and 2000 mg/kg bw/d groups (p 0= 0.01).
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Number of abortions:
not examined
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not examined
Changes in number of pregnant:
no effects observed
Key result
Dose descriptor:
NOAEL
Remarks:
maternal toxicity
Effect level:
125 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
Dose descriptor:
LOAEL
Effect level:
500 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
body weight and weight gain
Key result
Abnormalities:
no effects observed
Fetal body weight changes:
not examined
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
not examined
Changes in postnatal survival:
not examined
External malformations:
no effects observed
Skeletal malformations:
effects observed, non-treatment-related
Description (incidence and severity):
The incidence of fetuses with at least one ossification variation was significantly increased in the 2000 mg/kg/ bw/d group (p 0.05). Main variations were incomplete ossification of several cranial bones and vertebral elements and in addition in the 500 mg/kg bw/d group the incidence of rudimentary rib structures; a significant decrease of those variations in the 125 mg/kg bw/d group was not considered treatment related (p ≤0.05).
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
No treatment related increases in soft tissue malformations and variations were found.
Key result
Dose descriptor:
NOAEL
Effect level:
125 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Incomplete ossification of several cranial bones and vertebral elements and in addition in the 500 mg/kg bw/d group the incidence of rudimentary rib structures;
Key result
Abnormalities:
effects observed, treatment-related
Localisation:
other: see description
Description (incidence and severity):
The incidence of fetuses with at least one ossification variation was significantly increased in the 2000 mg/kg/ bw/d group (p 0.05): main variations were incomplete ossification of several cranial bones and vertebral elements and in addition in the 500 mg/kg bw/d group the incidence of rudimentary rib structures; a significant decrease of those variations in the 125 mg/kg bw/d group was not considered treatment related (p ≤0.05). the incidence of fetuses with at least one ossification variation was significantly increased in the 2000 mg/kg/ bw/d group (p 0.05): main variations were incomplete ossification of several cranial bones and vertebral elements and in addition in the 500 mg/kg bw/d group the incidence of rudimentary rib structures; a significant decrease of those variations in the 125 mg/kg bw/d group was not considered treatment related (p ≤0.05).
Key result
Developmental effects observed:
yes
Lowest effective dose / conc.:
500 mg/kg bw/day (actual dose received)
Treatment related:
yes
Relation to maternal toxicity:
developmental effects as a secondary non-specific consequence of maternal toxicity effects
Dose response relationship:
yes
Relevant for humans:
yes

Table 1: Incidence of Fetal Skeletal Alterations

Dose (mg/kg/day)

0

125

500

2000

Rudimentary ribs

20

(14)

15

(10)

48

(18)

52

(20)

Total fetuses (litters) with variations

82

(21)

54

(22)

82

(23)

106

(22)

% fetuses (litters) with variations

57.3 (91.3)

41.9 (95.7)

57.2

(100)

79.7

(100)

Conclusions:
Since no embryotoxicity was seen at doses that were not toxic to the maternal animals, the test substance is not classified as teratogenic.
Executive summary:

This OECD 414 study in compleance with GLP examined the potential developmental toxicity of the test substance. Groups of 24 mated female rats were exposed to concentrations of 0, 125, 500, and 2000 mg/kg bw/day of test substance by oral gavage during days 6 - 15 of gestation. On day 20 of gestation, the animals were sacrificed and the uterine contents examined. Pups were removed by caesarean section and soft tissue and skeletal examinations performed. The LOAEL for maternal toxicity was 500 mg/kg bw/day based on reduced body weight gain. The NOAEL for maternal toxicity was 125 mg/kg bw/day. The LOAEL for embryotoxicity was also 500 mg/kg bw/day based on increased incidence of incomplete ossification. The NOAEL for embryotoxicity was also 125 mg/kg bw/day. Since embryotoxicity was seen at doses that were toxic to the maternal animals, the test substance is not classified as teratogenic.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
125 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Key study is developmental study, reliable with restrictions.
Additional information

This study examined the potential developmental toxicity of the test substance. Groups of 24 mated female rats were exposed to concentrations of 0, 125, 500, and 2000 mg/kg bw/d of test substance by oral gavage during days 6-15 of gestation. On day 20 of gestation, the animals were sacrificed and the uterine contents examined. Pups were removed by caesarean section and soft tissue and skeletal examinations performed. The LOAEL for maternal toxicity was 500 mg/kg bw/day based on reduced body weight gain. The NOAEL for maternal toxicity was 125 mg/kg bw/day. The LOAEL for embryotoxicity was also 500 mg/kg bw/day based on increased incidence of incomplete ossification. The NOAEL for embryotoxicity was also 125 mg/kg bw/day. Since no embryotoxicity was seen at doses that were not toxic to the maternal animals, the test substance is not classified as teratogenic.

Justification for classification or non-classification

Based on the available information, the test substance is not classified for reproductive toxicity in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.

Additional information

Categories Display