Sulfuric acid, mono-C12-14 (even numbered)-alkyl esters, compds. with triethanolamine

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to Guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1976

Report date:

1976

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

yes

Remarks:

Some examinations like neurobehaviour are missing due to the year when the study was conducted.

GLP compliance:

no

Remarks:

pre-GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sulfuric acid, mono-C12-15-alkyl esters, sodium salts

EC Number:

272-575-8

EC Name:

Sulfuric acid, mono-C12-15-alkyl esters, sodium salts

Cas Number:

68890-70-0

IUPAC Name:

Sulfuric acid, mono-C12-15-alkyl esters, sodium salts

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: plain diet

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

Daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0, 0.07, 0.14, 0.28, 0.56, 1.13, 2.25%
Basis:
nominal in diet

Doses / concentrations 2

Remarks:

Doses / Concentrations:
62, 122, 245 488, 1016, 2081 mg/kg bw/day
Basis:
actual ingested

No. of animals per sex per dose:

10 test group
20 control group

Control animals:

yes, plain diet

Examinations

Observations and examinations performed and frequency:

BODY WEIGHT:
- Time schedule for examinations: Weekly

FOOD AND WATER CONSUMPTION:
- Time schedule for examinations: Twice weekly

HAEMATOLOGY:
- Time schedule for collection of blood: At the end of the experimental period (13 weeks)
- Anaesthetic used for blood collection: Yes (halothane)

CLINICAL CHEMISTRY:
- Time schedule for collection of blood: At the end of the experimental period (13 weeks)

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

effects observed, treatment-related

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

effects observed, treatment-related

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Clinical biochemistry findings:

effects observed, treatment-related

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
Two male rats were killed due to ill health during this study.

BODY WEIGHT AND WEIGHT GAIN
The two highest dose groups gained less weight.

FOOD AND WATER CONSUMPTION
The high dose groups ate less. High dose females drank less water.

HAEMATOLOGY
Serum protein decreased at the highest dose (males).

CLINICAL CHEMISTRY
Serum Mg, protein, cholesterol, decreased at the highest dose (males). Serum GOT was elevated in high dose males. Serum GPT, was elevated in males of the two highest dose groups (1.13% and 2.25%) and females of the second highest dose group (1.13%). Serum AP was increased in the 1.13% and 2.25% dose groups (females) and 1.13% group (males).

ORGAN WEIGHTS
Relative liver weights (both sexes) increased in the three highest dose groups (0.56%-2.25%). Absolute spleen weights increased in males at the two highest doses and females at the highest dose. Absolute kidney weights decreased in high dose males. Relative kidney weights increased in females at the two highest doses. Relative weights of the testes increased at the two highest doses.

GROSS PATHOLOGY
High dose males had virtually no abdominal fat and changes in color and consistency of intestinal contents. These findings were less frequently noted in high dose females.

HISTOPATHOLOGY: NON-NEOPLASTIC
Diffuse (6 females, 3 males) and periportal (11/20) hypertrophy, reduced cytoplasmic (glycogenic) vacuolation, reduced cytoplasmic neutral fat and hemodiderin content prominent at high dose. Periportal hypertrophy also observed at nest two highest doses (1.13% and 0.56%). Periportal parenchymal hypertrophy was observed in 4 females at the 0.28% level. reduced cytoplasmic (glycogenic) vacuolation, reduced cytoplasmic neutral fat and hemodiderin conten were observed at the 0.56%-2.25% dose levels.
Nephrocalcinosis is freqently observed in untreated females of the Wistar strain: the incidence and severity was reduced in the highest dose group.
Lymphatic dilation of the small intestine was more prominent at the high dose.

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

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

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Systemic effects that could not be regarded solely as adaptive processess, e.g. increased testes weight.

2

Dose descriptor:

LOAEL

Effect level:

1 016 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: Systemic effects that could not be regarded solely as adaptive processess, e.g. increased testes weight.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Since the liver as the target organ showed only adaptive responses, the NOAEL was set at 0.56% (488 mg/kg bw/day). The adaptive changes included elevated relative liver weight due to a lower body weight and reduced food consumption, hepatic periportal hypertrophy as well as increased serum alkaline phosphatase (AP) activity.
An increased serum AP activity is considered to represent a physiological adaptation resulting from changes in hepatic metabolism required for the breakdown and detoxification of the test material. Since AP is mainly localized in the hepatic parenchyma, enlargement of the hepatic parenchymal cells accompanied by an increased organ weight are an obvious consequence.