Stoddard solvent

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

review article or handbook

Title:

Teratology study in rats, Stoddard solvent

Author:

API

Year:

1983

Bibliographic source:

Final report (Litton Bionetics Inc. Project No. 20698-2). Washington, DC, American Petroleum Institute (Microfiche FYI-AX-0183-0232).

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

A Prenatal Development Toxicity Study equivalent or similar to OECD TG 414 was conducted using groups of 26 or 27 Sprague-Dawley female rats. Female rats were exposed by inhalation to white spirit (Stoddard solvent; boiling range, 157° to 204° C; 43% normal/branched aliphatics, 33% cyclic aliphatics, 24% aromatics) at concentrations of 0, 600, or 2400 mg/m3 (0, 100, and 400 ppm, respectively) for 6 hours per day on days 6 to 15 of gestation.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Stoddard solvent

EC Number:

232-489-3

EC Name:

Stoddard solvent

Cas Number:

8052-41-3

Molecular formula:

C10H22

IUPAC Name:

stoddard solvent

Test material form:

liquid

Specific details on test material used for the study:

Stoddard solvent; boiling range, 157° to 204° C; 43% normal/branched aliphatics, 33% cyclic aliphatics, 24% aromatics)

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Portage, MI
- Age at study initiation: 71 days
- Weight at study initiation: 261-264 g
- Housing: Individually housed in suspended stainless-steel cages with wire mesh floors and fronts- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 14 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 38-74
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

air

Details on mating procedure:

Impregnation procedure:
cohoused- If cohoused:
- M/F ratio per cage: 1:1
- Length of cohabitation: nightly
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: vaginal plug and/or sperm in vaginal smear referred to as day 0 of pregnancy

Duration of treatment / exposure:

days 6 to 15 of gestation

Frequency of treatment:

once daily

Duration of test:

up to day 3 post partum

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/m³ air

Doses / concentrations 2

Dose / conc.:

600 mg/m³ air

Remarks:

100 ppm

Doses / concentrations 3

Dose / conc.:

2 400 mg/m³ air

Remarks:

400 ppm

No. of animals per sex per dose:

26 and 27 animals per group

Control animals:

yes, concurrent vehicle

Details on study design:

A Prenatal Development Toxicity Study equivalent or similar to OECD TG 414 was conducted using groups of 26 or 27 Sprague-Dawley female rats. Female rats were exposed by inhalation to white spirit (Stoddard solvent; boiling range, 157° to 204° C; 43% normal/branched aliphatics, 33% cyclic aliphatics, 24% aromatics) at concentrations of 0, 600, or 2400 mg/m3 (0, 100, and 400 ppm, respectively) for 6 hours per day on days 6 to 15 of gestation.

Examinations

Statistics:

2x2 Coningency tables; Chi Square testcorrected for discontinuity using Yates correction; 2x2 tables,
Fisher 's exact Probability test, ANOVA, Kruskal-Wallis H test, Student's t-test

Indices:

Reproductive Index; Gestation Index; Viability Index

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:

effects observed, non-treatment-related

Mortality:

no mortality observed

Details on results:

No maternal toxicity or differences in litter size or average fetal weight were seen between the groups. There were no statistical differences for skeletal variations between the control group and the 100 ppm or the 400 ppm exposed group. The study director noted that pups in one litter in the 100 ppm group one litter in 400 ppm exposed groups had at least one unusual skeletal finding. The unusual variations were reduced ossification in various bones of the pups. The pups from these two litters had a significant reduced mean body weight when compared to control and to the mean of the treatment group:
Control mean body weight: 3.6 g;
100 ppm mean body weight: 3.7g, 100 ppm litter with unusual findings: 1.4g;
400 ppm mean body weight: 3.7g, 400 ppm litter with unusual findings: 2.0g.
The study concluded that the effects were considered expressions of retarded growth rather than malformations. Based on this information, the developmental NOAEC = 2400 mg/m3 or 400 ppm, the highest concentration tested.

Effect levels (maternal animals)

Dose descriptor:

NOAEC

Effect level:

2 400 mg/m³ air

Based on:

test mat.

Basis for effect level:

body weight and weight gain

clinical signs

Remarks on result:

other:

Remarks:

based on expressions of retarded growth and not malformations

Maternal abnormalities

Abnormalities:

not specified

Results (fetuses)

Fetal body weight changes:

effects observed, treatment-related

Details on embryotoxic / teratogenic effects:

No maternal toxicity or differences in litter size or average fetal weight were seen between the groups. There were no statistical differences for skeletal variations between the control group and the 100 ppm or the 400 ppm exposed group. The study director noted that pups in one litter in the 100 ppm group one litter in 400 ppm exposed groups had at least one unusual skeletal finding. The unusual variations were reduced ossification in various bones of the pups. The pups from these two litters had a significant reduced mean body weight when compared to control and to the mean of the treatment group:
Control mean body weight: 3.6 g;
100 ppm mean body weight: 3.7g, 100 ppm litter with unusual findings: 1.4g;
400 ppm mean body weight: 3.7g, 400 ppm litter with unusual findings: 2.0g.
The study concluded that the effects were considered expressions of retarded growth rather than malformations. Based on this information, the developmental NOAEC = 2400 mg/m3 or 400 ppm, the highest concentration tested.

Effect levels (fetuses)

Dose descriptor:

NOAEC

Effect level:

2 400 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

fetal/pup body weight changes

Remarks on result:

other:

Remarks:

based on significant reduced mean body weight when compared to control and to the mean of the treatment group

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

A Prenatal Development Toxicity Study equivalent or similar to OECD TG 414 was conducted using groups of 26 or 27 Sprague-Dawley female rats. Female rats were exposed by inhalation to white spirit (Stoddard solvent; boiling range, 157° to 204° C; 43% normal/branched aliphatics, 33% cyclic aliphatics, 24% aromatics) at concentrations of 0, 600, or 2400 mg/m³(0, 100, and 400 ppm, respectively) for 6 hours per day on days 6 to 15 of gestation. No maternal toxicity or differences in litter size or average fetal weight were seen between the groups. There were no statistical differences for skeletal variations between the control group and the 100 ppm or the 400 ppm exposed group. The study director noted that pups in one litter in the 100 ppm group one litter in 400 ppm exposed groups had at least one unusual skeletal finding. The unusual variations were reduced ossification in various bones of the pups. The pups from these two litters had a significant reduced mean body weight when compared to control and to the mean of the treatment group:

Control mean body weight: 3.6 g;

100 ppm mean body weight: 3.7g, 100 ppm litter with unusual findings: 1.4g;

400 ppm mean body weight: 3.7g, 400 ppm litter with unusual findings: 2.0g.

The study concluded that the effects were considered expressions of retarded growth rather than malformations. Based on this information, the developmental NOAEC = 2400 mg/m3 or 400 ppm, the highest concentration tested.

Applicant's summary and conclusion

Conclusions:

The study concluded that the effects were considered expressions of retarded growth rather than malformations. Based on this information, the developmental NOAEC = 2400 mg/m3 or 400 ppm, the highest concentration tested.

Executive summary:

A Prenatal Development Toxicity Study equivalent or similar to OECD TG 414 was conducted using groups of 26 or 27 Sprague-Dawley female rats. Female rats were exposed by inhalation to white spirit (Stoddard solvent; boiling range, 157° to 204° C; 43% normal/branched aliphatics, 33% cyclic aliphatics, 24% aromatics) at concentrations of 0, 600, or 2400 mg/m³(0, 100, and 400 ppm, respectively) for 6 hours per day on days 6 to 15 of gestation. No maternal toxicity or differences in litter size or average fetal weight were seen between the groups. There were no statistical differences for skeletal variations between the control group and the 100 ppm or the 400 ppm exposed group. The study director noted that pups in one litter in the 100 ppm group one litter in 400 ppm exposed groups had at least one unusual skeletal finding. The unusual variations were reduced ossification in various bones of the pups. The pups from these two litters had a significant reduced mean body weight when compared to control and to the mean of the treatment group:

Control mean body weight: 3.6 g;

100 ppm mean body weight: 3.7g, 100 ppm litter with unusual findings: 1.4g;

400 ppm mean body weight: 3.7g, 400 ppm litter with unusual findings: 2.0g.

The study concluded that the effects were considered expressions of retarded growth rather than malformations. Based on this information, the developmental NOAEC = 2400 mg/m3 or 400 ppm, the highest concentration tested.