Docusate sodium

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

1991

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Data source

Reference

Reference 1

Reference Type:

other: Submission of unpublished data by CTFA, 200 pp. Available for review from Director, Cosmetic Ingredient Review, 1101 17th Street, NW, Suite 310, Washington, DC 20036, USA.

Title:

Acute oral, ocular, primary dermal irritation, 21-day dermal irritation, photocontact allergenicity, 6 RIPTs, 13-week subchronic dermal, 13-week subchronic inhalation, four 4-day mini-cumulative irritation. Submission of unpublished data by CTFA, 200 pp.

Author:

Cosmetic, Toiletry, and Fragrance Association (CTFA).

Year:

1991

Bibliographic source:

CIR 1998, 2013 and 2016

Reference 2

Reference Type:

review article or handbook

Title:

Amended Final Report on the Safety Assessment of Dioctyl sodium sulfosuccinate.

Author:

CIR (Cosmetic Ingredient Review)

Year:

1998

Bibliographic source:

International Journal of Toxicology, 147(Suppl. 4):1-20,1998.

Reference 3

Reference Type:

review article or handbook

Title:

Re-review: Safety Assessment of Alkyl Sulfosuccinate Salts as Used in Cosmetics.

Author:

CIR Expert Panel

Year:

2013

Bibliographic source:

CIR Expert Panel Meeting June 10-11, 2013. Release Date: May 17, 2013.

Reference 4

Reference Type:

review article or handbook

Title:

Safety Assessment of Dialkyl Sulfosuccinate Salts as Used in Cosmetics. Tentative Amended Report for Public Comment.

Author:

CIR (Cosmetic Ingredient Review)

Year:

2013

Bibliographic source:

Tentative Amended Report for Public Comment. Release Date: June 20, 2013. Panel Meeting Date: September 9-10, 2013.

Reference 5

Reference Type:

publication

Title:

Safety Assessment of Dialkyl Sulfosuccinate Salts as Used in Cosmetics.

Author:

Cosmetic lngredient Review (CIR) Expert Panel: Monice M. Fiume , Bart Heldreth, Wilma F. Bergfeld, Donald V. Belsito, Ronald A. Hill, Curtis D. Klaassen, Daniel C. Liebler, James G. Marks Jr, Ronald C. Shank, Thomas J. Slaga, Paul W. Snyder, and F. Alan Andersen.

Year:

2016

Bibliographic source:

International Joumal of Toxicology 2016, Vol. 35(Supplement 3) 34S-46S. DOi: 10.1177/1091581816673808

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Sprague-Dawley rats, 12 male and 12 female, were exposed to an aerosol of a product containing an effective Dioctyl Sodium Sulfosuccinate concentration of 0.21%. The concentration of exposure was 4.2 mg/m3, and lasted 4 hours a day, 5 days a week, for 13 weeks. An equal number of rats were kept in a control chamber during this time.
During week 7, two rats from each group were killed and necropsied. At the end of the 13 weeks, the remainder of the animals were killed and necropsied.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Docusate sodium

EC Number:

209-406-4

EC Name:

Docusate sodium

Cas Number:

577-11-7

Molecular formula:

C20H38O7S.Na

IUPAC Name:

sodium 1,4-bis[(2-ethylhexyl)oxy]-1,4-dioxobutane-2-sulfonate

Specific details on test material used for the study:

aerosol of a product containing an effective diethylhexyl sodium sulfosuccinate concentration of 0.21% at an exposure concentration of 4.2 mg/m3

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

4 h/day, 5 days/wk

Doses / concentrations

Dose / conc.:

4.2 other: mg/m3

Remarks:

a product containing an effective diethylhexyl sodium sulfosuccinate concentration of 0.21% at an exposure concentration of 4.2 mg/m3

No. of animals per sex per dose:

12

Control animals:

yes, concurrent no treatment

Details on study design:

During week 7, two rats from each group were killed and necropsied. At the end of the 13 weeks, the remainder of the animals were killed and necropsied.

Results and discussion

Results of examinations

Details on results:

There were no statistically significant differences in dosed and control groups, attributable to Dioctyl Sodium Sulfosuccinate, for the following parameters: mean body weight gain, survival, appearance and behavior, urinalysis values, and microscopic lesions. The following significant differences were noted in hematologic parameters in treated rats as compared to control rats: elevated erythrocytic values in male rats at 7 weeks and depressed mean corpuscular hemoglobin concentration values in male rats at 13 weeks. Significant differences between dosed and treated rats in clinical chemistry parameters included: elevated serum glutamic pyruvic transaminase (SGPT) values in males at 13 weeks, depressed SGPT values in females at 7 weeks, depressed serum alkaline phosphatase (SAP) values in females at 13 weeks, and elevated glucose values in both the 7- and 13-week females. For the male rats, there was a significant difference in relative brain, liver, and testis weights. In females, there was a significant difference in the absolute, but not relative, heart weight. At 7 weeks, the lungs of animals necropsied were examined and stained with Oil Red O. One dosed male rat had some scattered foci of neutrophils along with an increase in the number of free alveolar macrophages.

Applicant's summary and conclusion

Conclusions:

Rats exposed to an aerosol of a product containing an effective diethylhexyl sodium sulfosuccinate concentration of 0.21% at an exposure concentration of 4.2 mg/m3, 4 h/day, 5 days/wk, for 13 wks, had significant changes in hematology and clinical chemistry parameters as compared to controls.

Executive summary:

Sprague-Dawley rats, 12 male and 12 female, were exposed to an aerosol of a product containing an effective Dioctyl Sodium Sulfosuccinate concentration of 0.21% (CTFA 1991). The concentration of exposure was 4.2 mg/m³, and lasted 4 hours a day, 5 days a week, for 13 weeks. An equal number of rats were kept in a control chamber during this time.

During week 7, two rats from each group were killed and necropsied. At the end of the 13 weeks, the remainder of the animals were killed and necropsied. There were no statistically significant differences in dosed and control groups, attributable to Dioctyl Sodium Sulfosuccinate, for the following parameters: mean body weight gain, survival, appearance and behavior, urinalysis values, and microscopic lesions. The following significant differences were noted in hematologic parameters in treated rats as compared to control rats: elevated erythrocytic values in male rats at 7 weeks and depressed mean corpuscular hemoglobin concentration values in male rats at 13 weeks. Significant differences between dosed and treated rats in clinical chemistry parameters included: elevated serum glutamic pyruvic transaminase (SGPT) values in males at 13 weeks, depressed SGPT values in females at 7 weeks, depressed serum alkaline phosphatase (SAP) values in females at 13 weeks, and elevated glucose values in both the 7- and 13-week females. For the male rats, there was a significant difference in relative brain, liver, and testis weights. In females, there was a significant difference in the absolute, but not relative, heart weight. At 7 weeks, the lungs of animals necropsied were examined and stained with Oil Red O. One dosed male rat had some scattered foci of neutrophils along with an increase in the number of free alveolar macrophages.

Reference:

Cosmetic, Toiletry, and Fragrance Association (CTFA). 1991. Acute oral, ocular, primary dermal irritation, 21-day dermal irritation, photocontact allergenicity, 6 RIPTs, 13-week subchronic dermal, 13-week subchronic inhalation, four 4-day mini-cumulative irritation. Submission of unpublished data by CTFA, 200 pp. Available for review from Director, Cosmetic Ingredient Review, 1101 17th Street, NW, Suite 310, Washington, DC 20036, USA.