Phenol, dodecyl-, branched, sulfurized

Endpoint summary

Description of key information

Oral:
Based upon the results of this study, the apparent NOAEL (no observable adverse effect level) for subacute toxicity & neurotoxicity was considered to be 200 mg/kg/day. This was then adjusted for presence of oil to relate to the Registration material, and the value adopted was 100mg/kg. 
Dermal:
Repeated dermal applications of the test material caused no observable toxicity, with the exception of a slightly increased incidence and severity of skin irritation when compared to controls. The NOAEL for this study is considered to be >250 mg/kg b.wt./day males and female rats, highest dose tested. This is then adjusted to relate to the Registration material at 50% concentration, so the NOAEL value adopted is 125 mg/kg. 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Database is adequate for characterisation for test material; good quality 422 and also 407. The original NOAEL in the study is 200mg/kg bw/day. The presence of oil in the test samples is then accounted for and ultimate NOAEL adopted for Registration material is 50% of the above value (100mg/kg bw/day).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

125 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Database is adequate for characterisation for test material. The original NOAEL is 250mg/kg bw/day. The presence of oil in the test samples is then accounted for and ultimate NOAEL adopted for Registration material is 50% of the above value (125 mg/kg)

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Study duration:

subacute

Species:

rabbit

Quality of whole database:

Adequate: 3 studies on similar materials.

Additional information

There are no available data for this endpoint for CAS: 96152-43-1, therefore studies from supporting, structurally similar substances have been used as for read-across purposes to address the endpoints. The NOAELs derived have been adjusted for the Registration material to account for the presence of oil.

Oral

- In the key study for repeat dose toxicity, oral exposure (Lamb, 1993, report number: WIL-187001), the study was conducted to the OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test) and GLP. This study was used as the key study to adress this endpoint as the substance was tested at the lowest dose levels and therefore is considered to give the worst case scenario for assessment purposes. The reliability rating for this study is 1, however this is being used as read across to a supporting substance as there was no available data to fulfil this endpoint for the test material and so the reliability rating will be reduced to 2, according to the criteria of Klimisch, 1997. This study is being used as read across from Phenol, tetrapropenyl-, sulfurized, carbonates, calcium salts, overbased CAS No. 122384-87-6/68784-26-9.

The following supporting study is also available:

- In the Schroeder, 1998 study (Huntingdon Life Sciences report number: 96-4084) the study was conducted according to OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents). The study was conducted in line with GLP.

The reliability rating for this study is 1, however this is being used as read across to a supporting substance as there was no available data to fulfil this endpoint for the test material and so the reliability rating will be reduced to 2, according to the criteria of Klimisch, 1997. The study is being used as read across to a structurally similar substance (Phenol, tetrapropenyl-, sulfurized, calcium salts; CAS No. 122384-85-4/68855-45-8). NOAEL = 300 mg/kg b.wt./day for males and females based on increased adrenal weights and increased food consumption without commensurate body weight gain.

A further repeat dose study (28 and 90d, Haas 2010) exists on a related material from 2010, however the study information does not add key information to that above, despite the longer duration, and the NOAELs are higher than those derived above.

Dermal

- In the key study for repeated dose toxicity, dermal exposure (Korenaga et al, 1986, report number: SOCAL 2319), the study was conducted to the OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study) and GLP. The reliability rating for this study would be 1, however this is being used as read across to a supporting substance as there was no available data to fulfil this endpoint for the test material and so the reliability rating will be reduced to 2, according to the criteria of Klimisch, 1997.

Other supporting studies available however are not considered to be as reliable and so the results are not used in a hazard conclusion.

- The Biodynamics study, 1981 was not considered the key study as it was conducted less recently than the above key study, there was no GLP data and no guideline was specified although it seems similar to OECD 410 with deviations. Deviations are as follows: Only 2 dose groups were used, dressing was only a paper towel, not gauze as specified in the OECD guideline and the test site was wiped with a paper towel, no solvent used to remove test material. A reliability rating of 2 was assigned according to the criteria of Klimisch, 1997. Treatment-related effects were evident in the low- and high-dose males treated with the test material as indicated by marked, statistically significant, dose-related decreases in the absolute and relative (organ/body weight ratios) weights of the testes (absolute weight decreases of approximately 70% and 80%) and epididymides (absolute weight decreases of approximately 40% and 50%) at the end of the treatment period. The results of the microscopic examinations indicated that the topical administration of 25% and 100% (w/v) of the test material, for the period used in this study, causes topical irritating skin lesions in both male and female rabbits. Male rabbits, receiving 25% and 100% (w/v) of the test material, had an increased incidence of aspermatogenesis, reduced numbers of spermatids and a diffuse tubular hypoplasia when compared to control males. These changes had not completely resolved themselves in the four week recovery rabbits receiving 25% and 100% (w/v) of the test material.

- The Biodynamics study, 1983 was not considered the key study as it was conducted less recently than the above key study and no guideline was specified although it seems similar to OECD 410 with deviations. Deviations are as follows: Only 2 dose groups were used there was no data on dressing or removal of test material at the test site and only males were used in this study, OECD specifies 5 males/females per dose. A reliability rating of 2 was assigned according to the criteria of Klimisch, 1997. Increased incidence of desquamation, red raised pustules and red raised areas of eschar noted in the high dose group animals when compared to the control group animals. At necropsy, 2 animals in each of the treated groups were noted to have scabs, sores or necrotic areas on the dorsal cervical skin. The Group 2 animals showed an increase in mean epididymal weights while the group 3 animals showed a decrease in mean epididymal weights when compared to control group animals. These findings are statistically significant.

Total bilirubin and total protein levels were decreased in group 2 animals when compared to the control group values. Total bilirubin and glucose levels and the albumin/globulin ratio were decreased in Group 3 animals when compared to the control group animals.

Inhalation

In accordance with column 2 of REACH Annex XI, section 8.6, it is considered justifiable to omit the inhalation study. The substance only exists in liquid form and it will not be aerosolized in its normal use pattern and is not anticipated to form small particles or droplets. As such testing via the inhalation route is not considered appropriate for this substance.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Systemic parental toxicity: increased pituitary weight. Also some neonatal toxicity at this level.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Repeated dermal applications of the test material caused no observable toxicity in the highest quality study, with the exception of a slightly increased incidence and severity of skin irritation when compared to controls.

Repeated dose toxicity: via oral route - systemic effects (target organ) neurologic: pituitary

Justification for classification or non-classification

The key toxicity values for repeated dose toxicity were above those requiring classification in accordance to Directive 67/548/EEC or the CLP Regulation (EC) No 1272/2008. Therefore classification was not considered to be necessary.