Sodium cumenesulphonate

Carcinogenicity

Description of key information

No evidence of carcinogenic activity.

The key studies are 2-year rat and mouse dermal exposure studies conducted under GLP.  Up to 240 mg (rats) and 727 mg (mice) sodium xylenesulfonate/kg body weight in 50% ethanol were dosed 5 days per week for 104 weeks. There were no treatment related incidences of mononuclear cell leukaemia, neoplasms, or non-neoplastic lesions of the skin and other organs. The increased incidence of epidermal hyperplasia may have been related to exposure to the test substance. 

The NOAEL for systemic toxicity and carcinogenicity was reported as 240 mg/kg bw/day for rats and 727 mg/kg bw/day for mice.

The NOAEL for local effects is considered to be 60 mg/kg bw/day, based on the findings from the rat study.

 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

carcinogenicity: dermal

Type of information:

other: published data

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

GLP compliance:

yes

Species:

mouse

Strain:

B6C3F1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Simonsen Laboratories, Inc (Gilroy, CA)- Age at study initiation: 7 weeks- Weight at study initiation: no data- Fasting period before study: no data- Housing: individually caged in polycarbonate cages changed once per week and rotated on stainless steel racks once every two weeks. Sani-chip hardwood chips and spun-bonded polyester cage filters. - Diet (e.g. ad libitum): ad libitum- Water (e.g. ad libitum):ad libitum- Acclimation period: 14 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 16.7 to 25.6- Humidity (%): 34 to 69- Air changes (per hr): 10 minimum- Photoperiod (hrs dark / hrs light): 12 / 12IN-LIFE DATES: From: December 20, 1990 To: December 18, 1992

Route of administration:

dermal

Vehicle:

ethanol

Details on exposure:

TEST SITE- Area of exposure: shaved interscapular skin- % coverage: no data- Type of wrap if used: no data - Time intervals for shavings or clipplings: no dataREMOVAL OF TEST SUBSTANCE- Washing (if done): no data- Time after start of exposure: no dataTEST MATERIAL- Amount(s) applied (volume or weight with unit): 46 to 128 microliters- Concentration (if solution): 50% of applied volume. Doses were 0, 182, 364 and 727 mg/kg bw- Constant volume or concentration used: yesVEHICLE- Justification for use and choice of vehicle (if other than water): test material beads up in distilled water- Amount(s) applied (volume or weight with unit): in the 46 to 128 microliters- Concentration (if solution): 50%- Lot/batch no. (if required): no data- Purity: no dataUSE OF RESTRAINERS FOR PREVENTING INGESTION: no data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Dose formulations were prepared every 2-3 weeks. HPLC at the beginning of the study and every 7-10 weeks thereafter.

Duration of treatment / exposure:

2 years

Frequency of treatment:

5 days per week

Remarks:

Doses / Concentrations:0, 182, 364 and 727 mg/kg bwBasis:analytical conc.

No. of animals per sex per dose:

50

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale: based on 17-day and 14-week range finding studies- Rationale for animal assignment (if not random): random

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes - Time schedule: twice daily- Cage side observations checked not in tableDETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: monthlyDERMAL IRRITATION (if dermal study): Yes - Time schedule for examinations: monthlyBODY WEIGHT: Yes - Time schedule for examinations: weekly through week 13 and montly thereafterFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): - Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data - Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No dataFOOD EFFICIENCY:- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not a drinking water studyOPHTHALMOSCOPIC EXAMINATION: No dataHAEMATOLOGY: No dataCLINICAL CHEMISTRY: No dataURINALYSIS: No dataNEUROBEHAVIOURAL EXAMINATION: No dataOTHER:

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

Kaplan-Meier, logistic regression analysis, life table test, FIsher exact test, Cochran-Armitage trend test, comparison of continuous variables, Dunnett and Williams test, Shirley and Dunn

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

OTHER FINDINGS - epidermal hyperplasia observed in males and females at two highest doses and in female controls.

Details on results:

Gross examination of all animals for pathology did not reveal any abnormalities. No consistent dietary induced changes that could be considered a toxic response were observed. Animals that showed significant loss of weight, development of tumors, or other evidence of abnormalities were sacrificed and tissues examined. The incidence of tumors and the common incidental diseases were similar in all dieting groups.

Relevance of carcinogenic effects / potential:

No evidence of carcinogenic activity

Dose descriptor:

NOAEL

Effect level:

>= 727 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effectsclinical signs; mortality; body weight; gross pathology; histopathology

Remarks on result:

other: Effect type: other: toxicity and carcinogenicity

Conclusions:

Test substance was found to be non-carcinogenic
NOAEL:727 mg/kg bw/day

Executive summary:

No evidence of carcinogenic activity

Reference 2

Endpoint:

carcinogenicity: dermal

Type of information:

other: published data

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

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

GLP compliance:

yes

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories, Inc (Gilroy, CA)
- Age at study initiation: 7 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: housed individually in polycarbonate cages; changed every week and stainless steel racks rotated every 2 weeks. Heat-treated hardwood chips and spun-bonded polyester cage filters
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 14 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24.4
- Humidity (%): 35-70
- Air changes (per hr): 10 per day minimum
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

dermal

Vehicle:

ethanol

Details on exposure:

TEST SITE
- Area of exposure: shaved interscapular skin
- % coverage: no data
- Type of wrap if used: no data
- Time intervals for shavings or clipplings: no data


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: no data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 85 to 357 microliters (volume adjusted for weights during the study)
- Concentration (if solution): 50% of applied volume; doses were 0, 60, 120 and 240 mg/kg bw
- Constant volume or concentration used: yes


VEHICLE
- Justification for use and choice of vehicle (if other than water): beading of test substance in distilled water
- Amount(s) applied (volume or weight with unit): as part of the 85-357 microliters
- Concentration (if solution): 50%
- Lot/batch no. (if required): no data
- Purity: no data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

HPLC at the beginning of the study and then every 7 to 10 weeks

Duration of treatment / exposure:

2 years

Frequency of treatment:

5 days per week

Post exposure period:

no data

Remarks:

Doses / Concentrations:
0, 60, 120 and 240 mg/kg bw
Basis: analytical conc.

No. of animals per sex per dose:

50

Control animals:

yes, concurrent no treatment

Details on study design:

-- Dose selection rationale: based on 17 day and 14 week range finding studies
- Rationale for animal assignment (if not random): random

Positive control:

no data

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations checked in table were not included.


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: monthly


DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: monthly


BODY WEIGHT: Yes
- Time schedule for examinations: weekly through week 13, monthly thereafter


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data


FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not a drinking water study


OPHTHALMOSCOPIC EXAMINATION: No data


HAEMATOLOGY: No data


CLINICAL CHEMISTRY: No data


URINALYSIS: No data


NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Statistics:

Kaplan-Meier, logistic regression analysis, life table test, FIsher exact test, Cochran-Armitage trend test, comparison of continuous variables, Dunnett and Williams test, Shirley and Dunn

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Description (incidence and severity):

OTHER FINDINGS - epidermal hyperplasia at the site of treatment in several females at the two hightest doses and in one control animal

Details on results:

Gross examination of all animals for pathology did not reveal any abnormalities. No consistent dietary induced changes that could be considered a toxic response were observed. Animals that showed significant loss of weight, development of tumors, or other evidence of abnormalities were sacrificed and tissues examined. The incidence of tumors and the common incidental diseases were similar in all dieting groups.

Relevance of carcinogenic effects / potential:

No evidence of carcinogenic activity

Dose descriptor:

NOAEL

Effect level:

>= 240 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects clinical signs; mortality; body weight; gross pathology; organ weights; histopathology

Remarks on result:

other: Effect type: other: toxicity and carcinogenicity

Dose descriptor:

NOAEL

Effect level:

>= 60 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Epidermal hyperplasia

Remarks on result:

other: Effect type: other: local effects on skin

Conclusions:

Test substance was found to be non-carcinogenic
NOAEL:240 mg/kg bw/day

Executive summary:

No evidence of carcinogenic activity

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

240 mg/kg bw/day

Study duration:

chronic

Species:

rat

Justification for classification or non-classification

Based on the hazard assessment of Sodium cumenesulphonate in section 2.1 and 2.2. in IUCLID 6., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:

 

 

Directive 67/548

Carcinogenicity

Carc. Cat. 1; R45 May cause cancer.

Carc. Cat. 1; R49 May cause cancer by inhalation.

Carc. Cat. 2; R45 May cause cancer.

Carc. Cat. 2; R49 May cause cancer by inhalation.

Carc. Cat. 3; R40 Limited evidence of a carcinogenic effect.

 

CLP

Carcinogenicity

Carc. 1A

 

It is concluded that the Sodium cumenesulphonate does not meet the criteria to be classified for human health hazards for Carcinogenicity.