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Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Study meets the criteria for Klimisch code 1, however as used in a read-across approach Klimisch 2 is chosen.
Justification for type of information:
REPORTING FORMAT FOR THE CATEGORY APPROACH
1. HYPOTHESIS FOR THE CATEGORY APPROACH
The read across follows Scenario 5 - Qualitatively and quantitatively similar effects are caused by a common compound, which is formed from all category members (as described in the 2017 Read-Across Assessment Framework document).
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
TARGET: Benzenesulfonic acid, di-C10-14-alkyl derivs., sodium salts
SOURCE: Sulfonic acids, petroleum, calcium salts, overbased
3. CATEGORY APPROACH JUSTIFICATION
Linear and non-linear or branched alkylbenzene sulfonates are anionic surfactants with molecules characterized by a hydrophobic (apolar) and a hydrophilic (polar) group. As a group of chemicals, they are generally mixtures of closely related isomers and homologues. Each molecule contains an aromatic ring sulfonated at the para position and attached to either a linear or a branched alkyl chain at any position except the terminal carbons. The sulfonate group is a common functional group present in each of the category members, and is expected to exhibit similar biological activities with little influence from the length of carbon chain. The cation components of the chemicals (e.g. calcium, magnesium, sodium, or barium) are not expected to contribute significantly to the toxicity.
4. DATA MATRIX
See Read Across document attached to CSR

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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

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:
6 hours followed by a 14 day recovery in the high dose satellite recovery group only. (daily)
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
o mg/kg bw
Basis:
nominal per unit body weight
Remarks:
Doses / Concentrations:
100 mg /kg bw
Basis:
nominal per unit body weight
Remarks:
Doses / Concentrations:
300 mg/kg bw
Basis:
nominal per unit body weight
Remarks:
Doses / Concentrations:
1000 mg/kg/day
Basis:
nominal per unit body weight
No. of animals per sex per dose:
5 Sprague Dawley CD rats/sex
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

Dermal irritation:
effects observed, treatment-related
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)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Under the conditions of this study, dermal application of this test material resulted in no signs of overt systemic toxicity.

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:
Under the conditions of this study, dermal application of this test material resulted in no signs of overt systemic toxicity.
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.