Benzene, C10-13-alkyl derivs.

Endpoint summary

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.