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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
There is no data available on skin sensitation studies with Acetoguanamine. According to Annex VII of REACH regualtion before new tests are carried out to determine the listed enpoints of this Annex all available in-vitro data, in-vivo data, historical human data, validated (Q)SAR-data and data from structurally related substances (read-across approach) shall be assessed first. Therefore a literatur research was performed to find in-vitro data, in-vivo data or historical human data on skin sensitation with Acetoguanamine. No records were found and in order to avoid unnecessary animal testing structurally related substances were searched. A structurally related substance is Benzoguanamine, for which data on skin sensitation was found. Because of the fact that a read-across approach is always endpointspecific it was evaluated with the help of the "endpoint specific guidance" of ECHA in chapter R.7.3 ("skin and respiratory sensitisation") whether a read across between Benzo- and Acetoguanamine is possible. According to this guidance "the skin sensitisation potential of a chemical is related to its ability to react with skin proteins to form covalently linked conjugates and recognition of these by the immune system. In the vast majority of cases, this is dependent on electrophilic reactivity of the skin sensitizer or a derivative produced (usually by oxidation) in vivo or abiotically (Barratt et al., 1977)." The guidance also states the most frequently encountered types of electrophile-nucleophile reactions in skin sensitisation: "Michael-type reactions, SN2 reactions, SNAr reactions, acylation reactions and Schiff-base formation. These chemical reaction mechanisms can serve as a means of describing the domain of applicability (the scope) of (Q)SAR or form the basis for grouping chemicals into chemical categories. " Regarding the structure of Benzo- and Acetoguanamine it can be assumed, that both substances show a likely chemical reactivity in the mentioned electrophile-nucleophile reactions and therefore a simaliar skin sensitising effect can be assumed. This is supported by similar physico-chemical parameters of both substances. According to the above mentioned guideline "although the main factors driving skin sensitation (and therefore the (Q)SAR) is the underlying premise of the electrophilicity of a chemical, other factors such as hydrophobicity encoded in the octanol/water partition coefficient (log P) may also be considered as playing a role in the modifying the sensitisation response observed." Aceto- and Benzoguanamine both have a logPow in the same range (logPow(Acetoguanamine)= -0.88; logPow(Benzoguanamine)=1.38), which means that they might show a likely skin penetration ability.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
no
GLP compliance:
yes
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:Harlan Laboratories, NL
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15-25 g
- Housing: group housing (Makrolon Type III)
- Diet (e.g. ad libitum): pelleted standard diet, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 45-65 %
- Air changes (per hr): no information available
- Photoperiod (hrs dark / hrs light): 12 / 12

Study design: in vivo (LLNA)

Vehicle:
dimethyl sulphoxide
Concentration:
2.5%, 5%, 7.5%
No. of animals per dose:
4

Results and discussion

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: Group 1 (control group): 1.00 Group 2 (2.5%): 1.44 Group 3 (5%): 1.11 Group 4 (7.5%): 1.09
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: Group 1 (control group): 225.6 Group 2 (2.5%): 325.5 Group 3 (5%): 251.0 Group 4 (7.5%): 245.5

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
The presented guideline study is reliable and adequate for the chemical safety assessment of 6-phenyl-1,3,5-triazine-2,4-diyldiamine. Based on the findings of the study the test substance is classified as not sensitising.
Executive summary:

There is no data available on skin sensitation studies with Acetoguanamine. In order to avoid unnecessary animal testing and to fullfill the claim of REACH regulation Annex VII ((Q)SAR-data and data from structurally related substances (read-across approach) shall be assessed first before new tests are carried out) related substances were searched.

A structurally related substance is Benzoguanamine, for which data on skin sensitation was found. The read-across approach was evaluated by the help of the "endpoint specific guidance" of ECHA in chapter R.7.3 ("skin and respiratory sensitisation"). For the evaluation see above in "Rationale for reliability".

The presented study according to OECD 429 ("Skin Sensitation: Local Lymph Node Assay") with Benzoguanamine is adequate for the chemical safety assessment. Based on the findings of this study no classification as sensitising is needed.