Distillates (coal tar), heavy oils

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

two-generation reproductive toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)

Deviations:

yes

Remarks:

- see below (principles of method)

Qualifier:

according to guideline

Guideline:

EPA OPP 83-4 (Reproduction and Fertility Effects)

Deviations:

yes

Remarks:

- see below (principles of method)

Principles of method if other than guideline:

Deviations from guideline:
- Treatment of P generation for 56 days instead of 70 days
– No observation of oestrous cycle
– No documentation of sex ratio prior to culling of litter size
– No assessment of sperm parameters
– No determination of required organ weights
– No histopathology on coagulating gland

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: SD Crl:CD® VAF/Plus®

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan, USA
- Age at study initiation: P-generation: 46 d
- Weight at study initiation: P-generation: Males: 150-190 g; Females: 119-144-x g

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

VEHICLE
- Concentration in vehicle: 2.5, 7.5, 15.0 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg bw

Details on mating procedure:

Duration of mating: maximally 21 d

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

Duration of exposure before mating: 56 days (P), >= 113 days (F1)
Duration of exposure in general: From beginning of the study until sacrifice of P, F1, and F2-generation (through mating, gestation, and lactation of P and F1). F1 offspring was not exposed starting at weanling age but at 35 days of age to reduce gavage-induced injuries.

Frequency of treatment:

1x/d

Details on study schedule:

--

Remarks:

Doses / Concentrations:
25, 75, 150 mg/(kg bw*d)
Basis:
actual ingested

No. of animals per sex per dose:

26 of each sex per group

Control animals:

yes, concurrent vehicle

Details on study design:

--

Positive control:

none

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes
All animals were observed for mortality and overt signs of toxicity twice every day. During each study week, a detailed clinical observation of each animal was performed and the findings recorded daily. F1 parental animals were observed daily beginning at 22 days of age. Animals not surviving to scheduled euthanasia were necropsied and, where practicable, the tissues were preserved in fixative. Any rat showing signs of severe debility or toxicity were euthanized for humane reasons and to prevent loss of tissues. Following parturition for the F1 and F2 litters, all P and F1 males were evaluated for fertility, euthanized and necropsied. Any P male that failed to sire a litter was evaluated for spermatogenesis by examination of the epididymis for the presence of sperm.

BODY WEIGHT: Yes
Weekly until evidence of copulation or until euthanasia. Mated females were weighed on gestation days 0, 6, 15 and 20 and on lactation days 0, 7, 14 and 21. Body weights for non-gravid females were recorded on the above presumed gestation days but were not included in summarisation during gestation.

FOOD CONSUMPTION
Individual food consumption was recorded weekly for all animals prior to mating,
not measured during the mating periods because the animals were cohabited at that time.
Following the mating periods: Recorded weekly for males until euthanasia.
Weekly food consumption measurement was resumed after the mating period for females without evidence of copulation until either delivery or until euthanasia.
Mated females: Recorded on the corresponding body weight days during the gestation and lactation periods.
Non-gravid females: Recorded as indicated above but was not included in summarisation during gestation.

Oestrous cyclicity (parental animals):

not performed

Sperm parameters (parental animals):

Parameters examined in P-males that failed to sire a litter:
- Testis weight
- Presence of sperm in epididymis

Litter observations:

--

Postmortem examinations (parental animals):

GROSS NECROPSY
- Gross necropsy consisted of [external and internal examinations including the cervical, thoracic, and abdominal viscera.]

HISTOPATHOLOGY (P, F1): Female: Vagina, uterus, ovaries; male: Testis, epididymis, seminal vesicle, prostate

ORGAN WEIGHTS (P,F1): Testis

HISTOPATHOLOGY on F1 not selected for mating, F2: Not performed, only gross necropsy with special attention on reproductive organs

Postmortem examinations (offspring):

--

Statistics:

--

Reproductive indices:

see Tale under "Any other information on results"

Offspring viability indices:

see Tale under "Any other information on results"

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Salivation was observed at 75 mg/(kg*d) and above in the F1 generation.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Dose-related decrease in body weight during the pre-mating period at all dose levels.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Dose-related decrease in body weight during the pre-mating period at all dose levels.

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

No test-article-related microscopic lesions observed in animals that were either euthanized at study termination or died during the study period

Other effects:

not examined

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

Decreased fertility and pregnancy indices in the F1 female parental rats at all dose levels, but not interpreted as a treatment-related effect: no dose-response relationship, also low in control group.

--

Dose descriptor:

NOAEL

Effect level:

25 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Dose descriptor:

LOAEL

Effect level:

75 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male

Basis for effect level:

other: hypersalivation, trend in pre-mating body- weight loss

Dose descriptor:

NOAEL

Effect level:

25 mg/kg bw/day (actual dose received)

Sex:

female

Dose descriptor:

LOAEL

Effect level:

25 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: reduced pre-mating body weight

Clinical signs:

effects observed, treatment-related

Mortality / viability:

mortality observed, treatment-related

Description (incidence and severity):

see table below

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Dose-related decrease in growth of the F1 generation starting at 25 mg/(kg*d) (see below)

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

The decrease in mean absolute testis weight is considered secondary to decreases in body weight and not a direct effect of the test article.

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Description (incidence and severity):

No test-article-related microscopic lesions observed in animals that were either euthanized at study termination or died during the study period

VIABILITY (OFFSPRING):
There was a significant reduction in the number of live F1 offspring in the mid (weak effect) and high dose (pronounced effect) groups.
There is no notable evidence of impairment of viability in F1-offspring (neonates of P) at 25 and 75 mg/(kg*d) (Tab. 19). No impairment of viability is notable in F2-offspring (neonates of F1) at 25 mg/kg, but at 75 mg/kg at day 0 (Report, Tab 24).

BODY WEIGHT (OFFSPRING):
There is dose-related mean body-weight reduction in the pup weight of the F1 generation at 14 to 21 d lactation (by about 10 %) at >= 25 mg/(kg*d) (Report, Tab. 20): not conclusive for the low-dose group and not considered as a pathologically relevant, adverse effect (see also high variation e.g. F1 + F2 controls).

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

25 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

75 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: reduced body weight during lactation

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

25 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LOAEL

Generation:

F2

Effect level:

75 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: reduced pup viability

Reproductive effects observed:

not specified

Table for repoductive toxicity study:

		Genera-tion	Control		Low dose		Medium dose			High dose
Pathology			m	f	m	f	m	f		m	f
Histopathological examination	No treatment-related findings
Reproductive Performance
Mating index	%	P	96.0	96.2	100	100	100	100		100	100
		F1	91.7	92.3	83.3	85.2	60.0*	60.0 **		82.6	87.0
Fertility index (m. fertile/m. paired) (f. pregnant/f. paired) (Tab. 18/23)	%	P	88.0	88.5	76.9	76.9	83.3	83.3		84.6	84.6
		F1	50.0	61.5	29.2	25.9*	28.0	28.0*		47.8	47.8
Pregnancy index (f. pregnant/f. mated)	%	P	--	92	--	76.9	--	83.3		--	84.6
(Tab. 18/23)		F1	--	66.7	--	30.4*	--	46.7		--	55
Number of implantation sites (Tab. 28 and 29)	Mean	P	14.0		13.4		13.2			12.5
		F1	11.5		12.3		12.5			9.4
Duration of pregnancy (Tab. 18 and 23)	Mean (d)	P	22.1		22.4		22.4			22.9
		F1	22.4		22.3		22.8			23.4
Litter size (Tab. 19 and 24)	Mean	F1	13.2		12.3		11.5			9.2* #
		F2	9.9		11.7		10.0			3.4** #
Live offspring (Tab. 19 and 24)	Mean	F1	13.0		12.2		11.1*			6,8**
		F2	9.6		11.1		7.3*  #			1.8**  #
Live birth index (d 0) (Tab. 19 and 24)	%	F1	98.6		99.1		96.1			73.7**
		F2	96.8		95.1		73.3*			51.6**
Viability index (d 4) (Tab. 19 and 24)	%	F1	98.5		94.4		85.4			76.9**
		F2	85.6		80.8		100			87.5
Weight of live pups on day of age 0 (Tab. 20/25)	Mean (g)	F1	6.1		6.0		5.7			5.9
		F2	6.2		5.8		6.0			6.2
Weight of live pups on day of age 14 (Tab. 20/25)	Mean (g)	F1	34.2		31.0**		29.0**			24.8**
		F2	31.0		32.6		27.6			23.9*
Weight of live pups on day of age 21 (Tab. 20/25)	Mean (g)	F1	56.4	53.6	51.4**	49.9*	46.3**	44.7**		39.8**	39.0**
		F2	51.1	48.4	53.3	51.1	46.1	44.5		39.3	38.0*
*significantly different from controls, p≤ 0.05
**significantly different from controls, p≤ 0.01
#  Note: in the report, Tab. 19 and 24, no statistical significance stated, and for 1.8 only p<0.05 given. This appears to be erroneous and is assumed to be p<0.05 and 0.01, respectively.

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

25 mg/kg bw/day

Species:

rat

Additional information

No data on toxicity to reproduction is available for the substance distillates (coal tar), heavy oils (anthracene oil high (> 50 ppm) BaP, AOH) itself. Data obtained originate from the closely related tar oil creosote.

Due to the similar production process (fractionated distillation of coal tar using overlapping conditions), composition of both tar substances correspond to each other. Major components are mid-range PAH for both substances (3- and 4-ring PAH) with some additional 2-ring PAH in creosote but not in AOH.

3- and 4-ring PAH are considered to contribute predominantly to the toxicity for reproduction of creosote. 2-ring PAH will not have a substantial additional effect. But in case they have, using creosote data to represent the developmental toxicity of AOH will result in overestimation of the developmental toxicity of AOH as worst case. Thus, use of creosote as supporting substance for the toxicity to reproduction of AOH is justified.

The results were obtained from the structure-related tar oil creosote. In a two-generation reproduction study (OECD 416), the overall LOAEL / NOAEL are 75 and 25 mg/(kg bw*d), respectively, based on decreased body weight gain in the two highest dose groups (in F1 parents) and during gestation in F0 parents and decreased litter size in the high dose group, decreased survival and an increase in the number of stillborns, and decreased body weight of live pups in the two highest dose groups (less than 10 % bw reduction in the low dose group).

No typical adverse effect on reproductive performance of either sex was noted; the adverse effects observed appear to relate to pre- and post-natal development of the offspring rather than impairment of fertility.

Short description of key information:
In a two-generation reproduction study (OECD 416), NOAELs of 25 mg/kg bw/day were determined for each the parent, F1, and F2 generation based on hypersalivation and decreased body weight gain (P), reduced body weight during lactation (F1), and reduced pup viability (F2).

Justification for selection of Effect on fertility via oral route:
No data for AOH itself. Results relate to the structure-related tar oil creosote providing evidence of reprotoxic effects

Effects on developmental toxicity

Description of key information

In a developmental/teratogenicity study, a NOAEL of 50 mg/kg bw/day was determined for maternal toxicity (body weight loss, reduced food consumption) and embryotoxicity (increased post-implantation loss, early resorptions). NOAEL for fetotoxicity (foetus length and weight) and for teratogenicity (morphological malformations) was found to be higher at 175 mg/kg bw/day.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

- Soft-tissue examinations only on 1/3 instead of 1/2 of the foetuses. Post-treatment period of five days prior to caesarean sect.: Acc. to OECD TG 414 (22 Jan. 2001), dosage should cover the whole pregnancy up to 1 d prior to scheduled caesarean sect.

Qualifier:

according to guideline

Guideline:

EPA OPP 83-3 (Prenatal Developmental Toxicity Study)

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: SD, Crl:CD® VAF/Plus®

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, Michigan, USA
- Age at study initiation: Approx. 13 weeks
- Weight at study initiation:210 – 278 g

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on exposure:

VEHICLE

- Concentration in vehicle: 2.5, 7.5, 22.5 mg/ml
- Amount of vehicle (if gavage):10 ml/(kg bw*d)

Analytical verification of doses or concentrations:

no

Details on mating procedure:

Mating period: Until detection of copulatory plug (= day 0 of gestation)

Duration of treatment / exposure:

Day 6-15 of gestation

Frequency of treatment:

1x/d

Duration of test:

Duration of exposure: Day 6-15 of gestation
Postexposure period: Day 16-20 of gestation.

Remarks:

Doses / Concentrations:
25, 50, 175 mg/(kg bw*d)
Basis:
actual ingested

No. of animals per sex per dose:

30 mated females

Control animals:

yes, concurrent vehicle

Details on study design:

--

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily on days 6-20

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 6, 9, 12, 16 and 20

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, days 0, 6, 9, 12, 16 and 20
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study) No


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: Number and location of viable and non-viable fetuses

Fetal examinations:

- External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No data

Litter size, number of dead foetuses, foetal weight, sex ratio, external alterations

Statistics:

--

Indices:

--

Historical control data:

--

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
175 mg/(kg*d) dosage level: weak maternal toxicity as evidenced by increased hair loss, body weight loss during the first subinterval of treatment (gestation days 6-9), inhibition in body weight gain during the treatment period (days 6-16) and throughout gestation (until day 20), and decreased food consumption. There was a decreasing trend only without clear statistical significance.
50 mg/(kg*d) dosage level or lower: No evidence of maternal toxicity.

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Dose descriptor:

LOAEL

Effect level:

175 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Developmental toxicity at the 175 mg/(kg*d) dosage level: Increased incidence in post-implantation loss (including three whole litter resorptions vs. one litter resorbed in the vehicle control and none in the other treated groups), and reduced number of live foetuses. No adverse effect was demonstrated for late intrauterine development of live foetuses at any dose.
No evidence of developmental toxicity was observed at the 50 mg/(kg*d) dosage level or lower.
One, six, seven, and seven foetuses showed malformations in one, three, six, and five litters for the control, low-, mid-, and high-dose groups, respectively. The incidences for the mid-, and high-dose levels were significantly higher than for the control group. Most of the observed malformations are fairly common in rats and the values obtained for the eye malformations in this study were within historical control range. After factoring out these common eye abnormalities, each type of the remaining malformations occurred in only one or two instances per group. Thus, the malformations were not considered to be test-article related.
Developmental variations that occurred did not follow a dose-related pattern.

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: embryotoxicity

Dose descriptor:

LOAEL

Effect level:

175 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: embryotoxicity

Dose descriptor:

NOAEL

Effect level:

175 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: fetotoxicity

Dose descriptor:

LOAEL

Effect level:

> 175 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: fetotoxicity

Dose descriptor:

NOAEL

Effect level:

175 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Dose descriptor:

LOAEL

Effect level:

> 175 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: teratogenicity

Abnormalities:

not specified

Developmental effects observed:

not specified

Table forMaternal Effects
Parameter	Control data		25   mg/(kg*d)	50 mg/(kg*d)	175 mg/(kg*d)	Dose-response + / –
	historical	study
Number of dams examined	716	30	30	30	30
Pregnant females		27	20	23	23
Pregnancies [%]		90.0	66.0	76.0	76.0	–
Clinical findings during application of test substance		13	15	11	17	–
Mortality of dams [%]	0	0	0	0	0	–
Body weight gain
day 0-6		34	34	32	30	–
day 6-9		2	5	3	-2	–
day 9-12		12	12	13	12	–
day 12-16		28	21	25	21	–
day 16-20		57	65	64	51	–
day 6-16		42	38	40	31	–
day 0-20	143	133	137	136	112	–
Final dam weight change minus weight of uterus	62	64	67	66	61	–
Food consumption [g/animal/day]
day 0-6		21.2	21.0	20.2	20.5	–
day 6-9		14.6	16.7	14.4	12.9	–
day 9-12		14.1	15.5	14.1	13.6	–
day 12-16		17.9	15.0	12.6*	9.8**	+
day 16-20		25.5	28.6	29.5	30.4	–
day 6-16		15.7	15.7	13.6	11.9**	+
day 0-20		19.4	19.9	18.8	18.2	–
Necropsy findings in dams dead before end of test		No deaths occurred before end of test.
* Significantly different from controls, p ≤ 0.05 ** Significantly different from controls, p ≤ 0.01

Table forDevelopmentalEffects Litter response (Caesarean section data)
Parameter	Controldata		25 mg/kg/ day	50 mg/kg/ day	175 mg/kg/ day	Dose-response + / -
	historical	study
Corpora lutea mean/dam	16.8	16.6	16.0	16.3	16.0	–
Implantations mean/dam	15.0	14.2	13.8	14.6	12.9	–
Resorptions total/number of dams	850/708	31/27	17/20*	25/23	59/23*	+
Number of foetuses/dam		13.0	13.0	13.5	10.3	–
Pre-implantation loss [%]		11.6	13.8	10.6	12.2	–
Post-implantation loss [%]	7.3	8.1	6.2	7.4	19.9	+
Total number of litters		26	20	23	20	–
Foetuses / litter		13.0	13.0	13.5	10.3	–
Live foetuses / litter ratio	13.9	13.0	13.0	13.5	10.3	–
Dead foetuses / litter ratio		0	0	0	0	–
Foetus weight (mean) [g]	3.4	3.3	3.5	3.3	3.2	–
Male foetuses		3.4	3.6	3.4	3.3*^1)	+
Female foetuses		3.3	3.3	3.2	3.2	–
Uterine weight (mean) [g]	76.3	72.0	69.5	70.0	61.4	–
Crown-rump length (mean)[mm]		35	36	35	35	–
Foetal sex ratio [state ratio m/f]	0.982	1.108	0.904	1.006	1.135	–
* Significantly different from controls, p ≤ 0.05 ^1)questionable, no effect on crown length, see also female values, considered biologically irrelevant
Table forMorphologicalEffects Examination of the foetuses(Report, Tab. 9 + 10, p. 42/43)
Parameter	Controldata		25 mg/kg/ day	50 mg/kg/ day	175 mg/kg/ day	Dose-response + / -
	historical	study
External malformations^*[%]	0.20	0.00	0.77	2.89^1)	1.27	–
Skeletal malformations^*[%]	0.93	0.00	0.81	4.35^1)	1.72	–
Visceral malformations^*[%]	0.41	0.58	2.21	1.33	2.50	–
Fetuses with malformations [%]*		0.58	3.8	3.9^2)	5.5
External variations^*[%]	0.01	0.00	0.00	0.00	0.00	–
Skeletal variations^*[%]	34.4	36.7	50.4	49.7	43.1	–
Visceral variations^*[%]	1.44	10.5	11.0	7.33	1.67	–

*Figures are not given in the original study but calculated from the number of observations and the number of examined foetuses in the respective category.

¹⁾The relatively high incidences are only determined by an accumulation of 11 different skeletal and external malformations within one foetus from doe No. 56513 (Report, Appendix C, p. 100).

²⁾Because of multi-fold malformations observed in two foetuses (one with 4 and a second with 2 defects), the percentage of the number of animals with malformations is lower than the total percentage of malformations (comp. Report,Appendix C, p. 98ff). Four other foetuses carried only one structural defect as in the other dose groups.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

50 mg/kg bw/day

Species:

rat

Additional information

Results were obtained from the structure-related tar oil creosote (see above). In a developmental/teratogenicity study (OECD 414), an increase in the incidence of post-implantation losses and a reduction in the number of live foetuses was seen at a dose of 175 mg/kg bw/day given orally to pregnant rats from gestation day 6 through 15. No adverse effect was demonstrated for late intrauterine development of live foetuses at any dose.

Justification for selection of Effect on developmental toxicity: via oral route:
No data for AOH itself. Results relate to the structure-related tar oil creosote providing evidence of maternal and developmental toxicity.

Justification for classification or non-classification

The test results above are accepted as relevant for the classification of anthracene oil (BaP =< 50 ppm). The adverse effects observed require the classification for potential hazards

--according to Directive (EU) 67/548/EEC as follows:

• for impairment of reproduction: Repr. Cat. 3; R 62:Possible risk of impaired fertility
• for impairment development of progeny: Repr. Cat. 3; R63: Possible risk of harm to the unborn child -- according toRegulation (EC) No 1272/2008 as follows:

-- according to Regulation (EC) No 1272/2008 as follows:

• for impairment of fertility, reproduction and development: Repr. 2, H361: Suspected of damaging fertility or the unborn child.