Ammonium dodecylbenzenesulphonate

Endpoint summary

Description of key information

No repeated dose toxicity data are available for the substance.. The endpoint's requirement was addressed with information from LAS Na. There are three studies with LAS Na: the lowest LOAEL is from the 6-month rat study (Yoneyama et al., 1972) with a LOAEL of 115 mg/kg bw.  The highest NOAEL below this LOAEL is from the 9-month rat study (Yoneyama et al., 1976) with NOAEL = 85 mg/kg bw, based on histological changes seen in the kidney. Based on the data from all the studies, an overall NOAEL of 85 mg/kg bw was considered as the most releveant, derived from a 9- month oral study and corresponding to the NOAEL closest to the lowest  oral LOAEL of 115 mg/kg bw.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

85 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

The database is considered sufficient to fulfil the specific requirement.

Organ:

blood

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No information is available on the repeated dose toxicity of LAS IPA. The endpoint was addressed with data from LAS Na and IPA.

LAS Na:

Male and female rats were exposed to LAS Na (125, 250, 500 mg/kg bw/day) orally by gavage daily for 28 days. The results showed suppressed body weight gain, differences in some serum biochemical measures when compared to the controls, and decreased (spleen, heart, thymus) or increased (liver) organ weights in the animals of the highest dose level. The resultant LOAEL and NOAEL values were 250 and 125 mg/kg bw/day, respectively (Ito et al., 1978).

In a 6-month toxicity test male and female rats were exposed to LAS Na (CAS 69669-44-9) in the diet daily: 40, 115, 340, 1030 mg/kg bw/day. Diarrhea, suppressed growth, increased cecal weight, and degeneration of renal tubes characterized the highest dose group. Similar but less severe signs were seen in other doses with the exception of the lowest dose of 0.07%, which showed no adverse effects related to exposure to LAS. The resultant LOAEL and NOAEL values were 115 and 40 mg/kg bw/day, respectively (Yoneyama et al., 1972).

In a 9-month toxicity study male and female rats were exposed to LAS Na (CAS 69669-44-9; 85, 145, 430 mg/kg bw/day) in drinking water daily. Body weight was suppressed in the highest dose. Significant decreases in transaminase activity and renal Na,K-ATPase was seen in the second group. The resultant LOAEL and NOAEL values were 145 and 85 mg/kg bw/day, respectively (Yoneyama et al., 1976).

IPA:

Information for IPA are only available in this 90 -day inhalation study. Male and female Sprague-Dawley rats were dosed for 6 hrs/day, 5 days/wk for approximately 13 weeks with ispropylamine (IPA) vapours, at analytical exposure concentrations of 20, 101, and 499 mg IPA per cubic meter in air. The results revealed reduced mean body weights of male animals in the high exposure group throughout most of the study period. The only significant change in hematology and clinical chemistry values, which were considered treatment-related was a decrease in serum glucose (high dose group females). No treatment-related gross pathological changes were detected.The only relevant microscopic change observed was inflammation of the nasal mucosa in females tested with 499 mg/m3. The NOAEC of the study was set at 100 mg/m3.

Extrapolating the inhalatory NOAEC to an oral NOAEL with a sRV for rats of 0.29 mg/m3 (for a 6 -h exposure), and with a pulmonary absorption at least as great as absorption across the GI tract, the oral NOAEL for IPA will be 29 mg/kg bw. Extrapolation from the inhalation to the oral route is not likely to underestimate toxicity and therefore, it is considered acceptable.

The molecular conversion of this NOAEL to a NOAEL for LAS IPA leads to a value of 189 mg/kg bw, which is much higher than the 85 mg/kg bw proposed for LAS Na (94 mg/kg bw after molar scaling). Therefore, the NOAEL of 85 mg/kg bw/day (94 mg/kg bw after scaling) recorded in the 9-month feeding repeated-dose oral toxicity study for LAS-Na was selected, as the NOAEL for LAS IPA.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

There are three repeated dose oral toxicity studies with LAS Na.  The lowest LOAEL is from the 6-month rat study (Yoneyama et al., 1972) with a LOAEL of 115 mg/kg bw.  The highest NOAEL below this LOAEL is from the 9-month rat study (Yoneyama et al., 1976) with NOAEL = 85 mg/kg bw, based on histological changes seen in the kidney. In view of the available information it is not possible to determine which single study among those is the most reliable or appropriate for the determination of a NOAEL. Therefore, based on the data from all the studies, an overall NOAEL of 85 mg/kg bw is proposed, which was derived from a 9- month oral study and corresponds to the NOAEL, which is closest to the lowest available oral LOAEL of 115 mg/kg bw. No oral repeated-dose toxicity studies are available for LAS IPA, or IPA

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

The only 90-day toxicity study available for IPA is via the inhalative route. The only histological treatment related adverse effect observed was a local effect on the nose, that is expected to be caused by isopropylamine (free amine) and not to the ammonium cation. Other effects seen were decreased body weights and decreased serum glucose in high level female animals, as well as increases in the adrenal weights. The NOAEC of the study for the systemic effects of IPA is set at 100 mg/m3.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:

Not relevant

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: cecum; urogenital: kidneys

Justification for classification or non-classification

Based on the results of the repeated dose toxicity studies, LAS IPA does not warrant for a STOT classification according to (CLP) Regulation (EC) No. 1272/2008 . Although adverse effects have been seen after repeated exposures of animals to LAS Na, and IPA, these were seen at dose levels above the classification criterion limit of 100 mg/kg bw (lowest LOAEL observed for LAS Na was 115 mg/kg bw).