Benzenesulfonic acid, di-C10-14-alkyl derivs., calcium salts

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

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

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: study meets the criteria for Klimisch code 1, however as used in a read-across approach Klimisch 2 is chosen.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)

Deviations:

no

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sulfonic acids, petroleum, calcium salts, overbased

EC Number:

272-213-9

EC Name:

Sulfonic acids, petroleum, calcium salts, overbased

Cas Number:

68783-96-0

IUPAC Name:

68783-96-0

Constituent 2

Reference substance name:

petroleum derived calcium salt, overbased

IUPAC Name:

petroleum derived calcium salt, overbased

Details on test material:

The test material described as a petroleum derived calcium salt, overbased, belongs to the chemical group aryl / alkyl sulfonates. The alkyl chain lengths are, however, unspecified.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Sprague Dawley CD rats, 8-9 weeks of age at initiation of treatment

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on exposure:

Route of administration: Dermal, 6 hour/day, to the clipped, unabraided, dorsal surface.
The test substance was applied undiluted to the clipped dorsal surface for periods of 6h per day of study. The material was held in place by a gauze patch secured with tape. After each exposure period the treated area was wiped. The procedure was repeated daily for 28d.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

6h per day for 28d, followed by a 14 day recovery period in the high dose satellite recovery group only.

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 mg/kg bw
Basis:
nominal per unit body weight

Doses / concentrations 2

Remarks:

Doses / Concentrations:
100 mg/kg bw
Basis:
nominal per unit body weight

Doses / concentrations 3

Remarks:

Doses / Concentrations:
300 mg/kg bw
Basis:
nominal per unit body weight

Doses / concentrations 4

Remarks:

Doses / Concentrations:
1000 mg/kg bw
Basis:
nominal per unit body weight

No. of animals per sex per dose:

5

Control animals:

yes, sham-exposed

Details on study design:

Control and treatment groups: 5 rats/sex in the control group, in each dose level and in the satellite recovery group at the 1000 mg/kg/day dose. The control group received no treatment (sham control). The test material was administered undiluted to the treated animal based on individual animal body weight.
- Dose selection rationale: Dose rangefinding study - Dose levels were selected based on results of a rangefinding study conducted at dose levels up to 1000mg/kg/day. No signs of toxicity were observed.
- Rationale for selecting satellite groups: not given
- Post-exposure recovery period in satellite groups: 14 days (high dose group):

Positive control:

none

Examinations

Observations and examinations performed and frequency:

clinical observations daily
dermal responses on days 0, 1, 4, 7, 11, 14, 18, 21, 25 and prior to blood collection on day 28
body weight and food consumption during treatment and recovery
Hematology and clinical chemistry at termination of treatment and recovery
Microscopic examination on all animals

Sacrifice and pathology:

full range of evaluations performed

Statistics:

ANOVA with Dunnets test, Kruskal-Walis, Dunns summed rank test , Jonkheere test for monotonic trend, Student's t-test

Body weight, food consumption, hematology and clinical chemistry parameters, organ weights and organ/body weight ratios were analyzed. Mean values of all dose groups were compared to control at each time interval. Tests included parametric ANOVA with a Dunnett’s test and regression analysis for linear response, non-parametric Kruskal-Wallis and Dunn’s Summed Rank Test, Jonckheere’s test for monotonic trend. A Student’s t-test was used to compare the satellite group’s main study termination and recovery blood values and organ weights.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

No mortality occurred during the study. Low incidences of very slight erythema, desquamation and / or pinpoint scabbing were observed sporadically in all treated animals. All animals were free of edema during the study. Body weights and food consumption were unremarkable. There were no treatment related differences in heamatology. Differences from control were noted for several heamatology parameters including a statistically significant increase in mean % of neutrophils of 300 and 1000 mg/kg females and a decrease in mean % of lymphocytes in the 1000mg/kg females compared to controls on day 28. In the absence of differences from control in absolute white blood cell counts, these findings were not considered related to treatment. There was a statistically significant decrease in mean corpuscular haemoglobin concentration in the male satellite animals from day 28-42. In the absence of other significant findings these small differences were not considered clinically significant. Serum chemistry values were unremarkable. Gross postmortem findings were considered incidental and unrelated to treatment. There were no alterations in organ weights that were attributed to treatment.There were no test material related microscopic findings noted in any group. Effects on the skin were seen in all groups including control but tended to increase in male treated animals and females in the 300 and 1000 mg/kg groups, indicating a mild irritant effect of the test article.

Effect levels

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (nominal)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

A NOAEL of 1000 mg/kg was established for this study. No mortality occurred during this study. Low incidences of very slight erythemia, desquamation and/or pinpoint scabbing were observed sporadically in the treated animals. All animals were free of edema during the study. Body weights and food consumption data were unremarkable during the treatment and recovery periods. There were no treatment-related differences from control observed in the hematology data of the treated animals following the dosing or recovery periods. Differences from control were noted for several hematology parameters including a statistically significant increase in the mean percentage of neutrophils of the 300 and 1000 mg/kg females and a decrease in mean percentage of lymphocytes in the 1000 mg/kg females compared to control on day 28. There was a statistically significant decrease in mean percentage of basophils in the satellite females from day 28 to 42. However these values were within the normal range. In the absence of differences from control in absolute white blood cell counts, these findings were considered unrelated to treatment. There was a statistically significant decrease in the mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration of the male satellite animals from day 28 to 42. In the absence of other significant findings in mean hemoglobin or red blood cell parameters, these small differences were not considered clinically significant. Serum chemistry values were unremarkable in the treated animals at termination of the treatment and recovery periods. There was a slight increase in the mean aspartate aminotransferase and alanine aminotransferase of the high dose females at day 28. These increases were attributed to two females with high values. Similar changes were not observed in the satellite females or in the males at day 28. These increases were not considered related to treatment. There were several differences from control noted at the end of recovery. These values were within the range of normal and similar differences were not evident at the end of the treatment period indicating that these findings were not clinically significant or treatment related. Gross postmortem findings were limited to one 300 mg/kg male with small testes, one control female with discolored lungs and liver and black material in the stomach; and single occurrences of scabs in the 100 and 1000 mg/kg and recovery males. These findings were considered incidental and unrelated to treatment. Tape irritation was observed in a number of animals. There were no alterations in organ weights that were attributed to treatment with the test material. Slight alterations were noted in several organ weights at termination of dosing or recovery. There was a statistically significant decrease in mean absolute brain weight of the 300 mg/kg females compared to control. This finding lacked a dose response and was not considered biologically significant. There was a statistically significant decrease in mean relative adrenal and testes weights of the male satellite animals at termination of recovery compared to control at end of treatment. Compared to the high dose at study termination there was a statistically significant decrease in mean relative adrenal, brain and testes weight of the male satellite animals and mean relative adrenal and brain weight of the female satellite animals at recovery termination. These alterations in organ weights were attributed to the cessation of the stress associated with wrapping (adrenal) and the animals continued increase in body weight while organ weights remained constant in adult animals. In the absences of significant organ weight findings following treatment or correlating effects with histopathology these findings were not considered clinically significant. There were no test material related microscopic findings noted in any group. Livers from female rats of all groups (including control) sacrificed after 28 days of treatment exhibited focal necrosis. This finding did not exhibit a dose response. This finding has been seen in other dermal studies and has been attributed to trauma and/or ischemia to the liver resulting from the wrapping and manipulation of the animals. Liver necrosis was not evident in any of the satellite recovery animals. This finding was not considered treatment related. The treated skin of most animals revealed variable amounts of thickening of the epidermis due to acanthosis and hyperkeratosis, sebaceous gland hyperplasia and focal dermal inflammation. These changes occurred in all groups including control. However the severity of these changes tended to be increased in the male treated group rats and in the females of the 300 and 1000 mg/kg groups, suggesting a mild irritating effect of the test material. Following recovery these findings were less severe.

Applicant's summary and conclusion

Conclusions:

No evidence of systemic toxicity via the dermal route.

Executive summary:

The test substance exhibited no evidence of systemic toxicity via the dermal route under the conditions of this study when 5 Sprague Dawley CD rats/sex were exposed to the calcium sulfonate read across substance (CAS 68783 -96 -0) over a period of 28 days. A NOAEL of 1000 mg/kg was established for this study. Under the conditions of this study, dermal application of this test material resulted in no signs of overt systemic toxicity.