4-chlorophenol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

one-generation reproductive toxicity

Remarks:

based on generations indicated in Effect levels (migrated information)

Type of information:

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

Adequacy of study:

key study

Study period:

1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data from review article (report on chlorophenols - systematic review and critical evaluation of relevant data). Basic data given.

Principles of method if other than guideline:

Reproductive toxicity study - (long-term) oral exposure

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: drinking water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

ca. 6 months (pre-and postnatal exposure of progeny)

Details on study schedule:

Dams were exposed from 3 weeks of age through gestation gestation (bred at day 90 d) and lactation (12-14/group).

The progeny from each dose regime was continued on treatment from three weeks of age (weaning) until tumour development, death or termination of the study at 24 months (24-28 animals of each sex/group).

Eight randomly selected pups from each group were weaned at 3 weeks of age and continued on treatment for 10-15 weeks.

Remarks:

Doses / Concentrations:
500 mg/L
Basis:
nominal in water
(equivalent to 50 mg/kg bw/d)

Remarks:

Doses / Concentrations:
50 mg/L
Basis:
nominal in water
(equivalent to 5 mg/kg bw/d)

Remarks:

Doses / Concentrations:
5 mg/L
Basis:
nominal in water
(equivalent to 0.5 mg/kg bw/d)

Control animals:

yes, concurrent vehicle

Positive control:

Not applicable.

Parental animals: Observations and examinations:

BODY WEIGHT: Yes
- Time schedule for examinations: Body weight gain prior to breeding

OTHER:
- Maternal toxicity (body weight gain prior to breeding)

Litter observations:

REPRODUCTIVE PERFORMANCE
- conception

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
- litter size [live and stillborn]
- number of of stillborn
- birth weight
- survival to weaning
- weaning weight

Postmortem examinations (offspring):

SACRIFICE / EFFECT ON THE PROGENY
- body weight gain
- weight of thymus
- spleen and liver at termination
- haematology (red and white blood cell counts, packed cell volume, mean corpuscular volume, haemoglobin)
- immunocompetence (cell-mediated immunity, humoral immunity, number and phagocytic activity of peritoneal macrophages) at termination

- Maternal toxicity was not observed at any concentration tested.

Dose descriptor:

NOAEL

Remarks:

maternal

Effect level:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No maternal toxicity.

Dose descriptor:

NOAEL

Remarks:

reproduction

Effect level:

5 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Litter size decreased and the number of stillborn increased at 500 mg/L.

- Extension of the exposure of the dams through lactation, followed by exposure of the progeny for additional 10 - 15 weeks, did not result in effects on the progeny expossed both pre-and postnatally (at any concentration).

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

5

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: After 52 weeks: Increased red blood cell count, packed cell volume, and haemoglobin content.

Reproductive effects observed:

not specified

However, according to ATDR (1999), there is limited evidence that 2 -chlorophenol may reduce litter sizes when administered to rats in drinking water (Exon and Koller 1985).This effect was significant only at p≤0.1 and was observed at doses that caused other effects (e.g., increased liver weights, decreased delayed-type hypersensitivity).

Reference: ATDR, 1999. Toxicological profile for Chlorophenols, U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, July 1999, p. 126. [external reference]

Effect on fertility: via oral route

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

5 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

Estimated Klimisch Rating: 2

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Based on a two-year chronic drinking-water study with 2-chlorophenol (2-MCP) (read-across), in a screening test rats were exposed at dose rates of 0.5, 5, 50 mg/kg bw/d (pre-and postnatal exposure of progeny). Maternal toxicity was not observed at any concentration tested (P generation). The NOAEL for reproductive toxicity was deemed as 5 mg/kg bw/d. Furthermore, extension of the exposure of the dams through lactation, followed by exposure of the progeny for additional 10 - 15 weeks, did not result in effects on the progeny exposed both pre-and postnatally (at any concentration; F1 generation).

Short description of key information:
No data are available on the test substance. However, some data are available for 2-chlorophenol (2-MCP) based on a screening test in rats (drinking-water study) with 0.5, 5, 50 mg/kg bw/d. No maternal toxicity was observed at a dosage of 50 mg/kg bw/d. The NOAEL for reproductive toxicity was deemed as 5 mg/kg bw/d.

Justification for selection of Effect on fertility via oral route:
Data from review article (report on chlorophenols - systematic review and critical evaluation of relevant data). Basic data given.
The substance in the test was 2-chlorophenol.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

Due to the DSD classification (Table 3.2) and Seveso II Data, the test substance is considered not to be classified under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

 

Based on the harmonized classification – Annex VI – Regulation (EC) No 1272/2008, the test substance is considered not to be classified under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation No 605/2014.