4-chlorophenol

Toxicity to reproduction

Administrative data

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.

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Unnamed

Year:

1991

Report date:

1991

Reference 2

Reference Type:

review article or handbook

Title:

Chlorophenols other than pentachlorphenol (environmental health criteria 93)

Author:

EHC

Year:

1989

Bibliographic source:

http://www.inchem.org

Reference 3

Reference Type:

publication

Title:

Toxicity of 2-chlorophenol, 2,4-dichlorophenol, and 2,4,6-trichlorophenol.

Author:

Exon JH, Koller LD

Year:

1985

Bibliographic source:

In: Jolley, R.L, Bull, R.J., Davis, W.P., Katz, S., Roberts, M.H., Jr, & Jacobs, V.H., ed. Water chlorination: Environmental impact and health effects, Chelsea, Michigan, Lewis Publishers Inc., Vol. 5, pp. 307-330.

Reference 4

Reference Type:

publication

Title:

Alteration of transplacental carcinogenesis by chlorinated phenols.

Author:

Exon JH, Koller LD

Year:

1981

Bibliographic source:

In: Jolley, R.L., Brungs, W.A., Cotruvo, J.A., Cumming, R.B., Mattice, J.S., & Jacobs, V.A, ed. Water chlorination: Environmental impact and health effects, Ann Arbor, Michigan, Ann Arbor Science Publishers, Vol. 4, Book 2, pp. 1177-1188.

Materials and methods

Principles of method if other than guideline:

Reproductive toxicity study - (long-term) oral exposure

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-MCP

IUPAC Name:

2-MCP

Constituent 2

Reference substance name:

2-chlorophenol

EC Number:

202-433-2

EC Name:

2-chlorophenol

Cas Number:

95-57-8

IUPAC Name:

2-chlorophenol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

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.

Doses / concentrations

Doses / concentrations 1

Remarks:

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

Doses / concentrations 2

Remarks:

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

Doses / concentrations 3

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.

Examinations

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

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

- Maternal toxicity was not observed at any concentration tested.

Effect levels (P0)

1

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.

2

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.

Results: F1 generation

Details on results (F1)

- 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).

Effect levels (F1)

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.

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

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]