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Description of key information

The skin sensitizing potential of MBTS was confirmed in a modified Local Lymph Node Assay (LLNA) (De Jong 2002) and in guinea pig maximization tests ((Kaniwa 1992, Nakamura 1994). However, no skin sensitizing potential of MBTS was revealed in a Repeated Insult Patch Test with human volunteers (Monsanto Co. 1982); whereas several case report data indicated a skin sensitizing potential of MBTS in human (BUA report 1995). The above discussed data demonstrated a skin sensitization potential of MBTS. In consequence, existing classification with Skin Sens. category 1 is confirmed.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptable, well-documented publication which meets basic scientific principles
Principles of method if other than guideline:
Local lymph node assay (using ex vivo labeling of proliferating lymph node cells, according to Kimber and Weisberger 1989 Arch. Toxicol. 63, 274-282, Vanebriel et al 2000 Toxicol. Appl. Pharmacol 162, 77-85, Van Och et al. 2000 Toxicology 146, 49-59
GLP compliance:
no
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
Balb/c
Sex:
female
Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
no data
No. of animals per dose:
3 per dose group, control 6
Parameter:
SI
Remarks on result:
other: EC3: 2.9%

MBTS: EC3*: 2.9 % (L05 -L95: 1.4 - 6.7, estimated 90% confidence interval based on 200 bootstrap runs)

*effective concentration inducing a stimulation index of 3 in LLNA

Moderate skin sensitzing

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Executive summary:

The test substance MBTS is classified as skin sensitiser according regulation no. 1272/2008 (GHS).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The skin sensitzing potential of MBTS was evaluated in an acceptable documented modified Local Lymph Node Assay (LLNA) (De Jong 2002). A modified LLNA with ex vivo tritium thymidine (3H-TdR) labelling of the proliferating lymph node cells was used for the evaluation. Young adult female BALB/c mice (3 per dose group) were used in this modified LLNA; test substance solution was daily applied for three consecutive days (day 0, 1 and 2). A concurrent solvent control (AOO) was also included (6 animals). At day 5 following start of treatment animals were sacrificed and draining lymph nodes were excised. The local lymph nodes were weighed and single cell suspensions were prepared. These cells were cultured in presence of tritium thymidine (3H-TdR) to determine cell proliferation of the prepared lymph nodes per animal. The EC3 (effective concentration inducing a 3-fold increase in proliferation of lymph node cells) was calculated with non-linear regression analysis. For the MBTS an EC3 value of 2.9% was calculated by extrapolation of the experimental results. Based on this calculation a moderate skin sensitizing potential of MBTS is suggested.

The skin sensitizing potential of MBTS was also confirmed in guinea pig maximization tests. MBTS showed skin sensitizing effects in maximization tests according to Magnusson & Kligman (Kaniwa 1992, Nakamura 1994).

No skin sensitizing potential of MBTS was revealed in a Repeated Insult Patch Test with 53 human volunteers (Monsanto Co. 1982). During the induction phase a series of twelve applications, each of 24 hours duration, were performed over a period of three weeks. The test substance MBTS was applied as a 70% solution in petrolatum onto the back of the volunteers. After a rest period of two weeks the challenge was performed, a series of four applications each of 24 hour duration were performed within one week. Readings were performed after the 24 hour treatments. The test substance was negative in the Repeated Insult Patch Test, 0/53 volunteers with positive skin reactions.

Several case reports of eczema patents indicated a skin sensitizing potential of MBTS in humans (for review see BUA report1995). However, the patients, who in some cases reacted positively to MBTS in the patch test, were often hypersensitive to other rubber ingredients as well, especially MBT. The cross-reactivity between MBT and MBTS can probably be explained by the conversion of MBTS to MBT in the presence of reducing thiol groups.


Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification for Skin Sens. 1 ( H317: May cause an allergic skin reaction) is justified.