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Administrative data

Description of key information

Acute oral toxicity: LD50 (rat, males) > 4240 mg a.i./kg bw; equivalent to OECD guideline 401; pre-GLP study
Acute inhalation toxicity: no relevant route of exposure
Acute dermal toxicity: LD50 (rat, male/female) > 2000 mg/kg bw; OECD guideline 402; GLP

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions. Study performed before implementation of GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Study performance before implementation of the corresponding international OECD guideline 401. However, in consideration of the test institute, it can be anticipated, that study performance complies to a large extent to the later implemented international guideline. The test animals were not fasted before study initiation; in the lower dose group only 3 animals were used.
GLP compliance:
no
Remarks:
Study performed before implementation of GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: no data
- Weight at study initiation: 90 to 120 g
- Fasting period before study: nonfasted
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
- no vehicle

MAXIMUM DOSE VOLUME APPLIED:
- no data

DOSAGE PREPARATION (if unusual):
- no data

Doses:
5.0, 10.0 mL/kg
No. of animals per sex per dose:
3 for 5.0 mL/kg dose group, 10 for 10.0 mL/kg dose group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing on day 1 and at termination; observation of clinical signs 0-6 h, 6-24 h, days 2, 3, 4, 5, 6, 7, 8-14
- Necropsy of survivors performed: yes
- Other examinations performed: no data
Statistics:
none
Sex:
male
Dose descriptor:
LD50
Effect level:
> 10 600 mg/kg bw
Based on:
other: product
Remarks on result:
other: mortality 1/10; recalculation to mg/kg bw with density=1.06 g/cm³
Sex:
male
Dose descriptor:
LD50
Effect level:
> 4 240 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: mortality 1/10; recalculation to mg/kg bw with density=1.06 g/cm³
Mortality:
- 0/3 died in the 5.0 mL/kg dose group
- 1/10 died in the 10.0 mL/kg dose group within in first 6 hours after application
Clinical signs:
- all animals were sluggish in the 10.0 mL/kg dose group within the first 6 hours after application, the survivors had recovered on day 2
- no signs in the 5.0 mL/kg dose group
Body weight:
- mean body weight in 5.0 mL/kg dose group: day 1: 108 g, termination: 200 g
- mean body weight in 10.0 mL/kg dose group: day 1: 106 g, termination: 192 g
Gross pathology:
All survivors appeared normal.
In the dead animal the stomach was transparent and filled with liquid; the intestines appeared pink and injected.
Other findings:
none reported
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
On the basis of the results obtained after a single oral administration, the oral LD50 was determined to be > 10600 mg/kg body weight based on product, corresponding to approximately > 4240 mg/kg bw referring to 100 % active ingredient.
Executive summary:

In an acute oral toxicity study, groups of nonfasted male Wistar ratswere given a single oral dose of MAPTAC (40% by weight in water) at doses of  5.0 and 10.0 mL/kg bw corresponding to 5300 and 10600 mg/kg bw, respectively based on a density of 1.06 g/cm³, and observed for 14 days. 3 animals in the lower dose group and 10 animals in the higher dose group were used.

No mortality occurred in the 5 mL/kg dose group; 1/10 died in the 10.0 mL/kg dose group. Sluggishness was observed in the higher dose group up to 6 hours after dosing, but all surviving animals had recovered on day 2. No abnormalities were observed at necropsy in the surviving animals.

Oral LD50 Males > 10600 mg/kg bw

The LD50 determined refers to the test substance as delivered by the sponsor. The amount of active ingredient in the test substance is 40%. Therefore the calculated oral LD50 referring to 100% active ingredient is > 4240 mg/kg bw.

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 240 mg/kg bw
Quality of whole database:
One relevant, reliable (Klimisch score = 2) and adequate study is available.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-09-20 to 2011-11-10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study. GLP.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 24 Feb 1987
Deviations:
yes
Remarks:
1 animal was subject to reduced exposure time ranging between >4 to 24 hours
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted 30 May 2008
Deviations:
yes
Remarks:
1 animal was subject to reduced exposure time ranging between >4 to 24 hours
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted August 1998
Deviations:
yes
Remarks:
1 animal was subject to reduced exposure time ranging between >4 to 24 hours
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: males: approx. 13 weeks; females: approx. 14 weeks
- Weight at study initiation: males: 246-257 g; females: 208-228 g
- Fasting period before study: no
- Housing: individual IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 091110)
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 1956)
- Water (e.g. ad libitum): tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%):55 ± 10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 2011-09-20 to 2011-11-10
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Remarks:
test substance in aqueous solution as delivered by the sponsor
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: at least 10%
- Type of wrap if used: gauze-dressing and non-irritating tape, fixed with additional dressing in suitable manner

REMOVAL OF TEST SUBSTANCE
- Washing (if done): tap water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): 50.6% (correction factor used for correct dose application: 1.976)

VEHICLE
Test substance applied as delivered by the sponsor
Duration of exposure:
24 hours (except for one female rat which unwrapped itself overnight, thus leading to a reduced duration of exposure of 4-24 hours)
For the animal which unwrapped itself, no signs of toxicity and significant dermal irritation were observed. As at the 4 h control observation the dressing was tight on all animals, it is very likely that the animal unwrapped itself clearly after the 4 h period. It can be expected that this animal has been exposed to the test item partially also by the oral route, while grooving, in addition to the dermal route.
It is concluded that the abbreviated exposure period has no effect on the overall result and the classification of the test item, and that a sufficient estimation of the dermal toxicity is ensured.
The validity of the study is not affected and according to animal welfare reasons it was decided not to repeat the study.
Doses:
2000 mg/kg bw (corrected for a.i.)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observation several times on day of dosing (at least once during first 30 minutes and with special attention given during the first 4 hours post-dose). Symptoms were recorded as soon as noticed. Thereafter, daily observations for clinical signs until end of observation period. All abnormalities were recorded. Animals were weighed on day 1 (prior to application of dose) and on day 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed:
-- In case of gross pathological changes, tissues were preserved for a possible histopathological evaluation.
-- The treated areas of skin were examined daily for signs of primary skin irritation. Signs of erythema and oedema were assessed using the scoring system laid down in OECD Guideline 404, adopted 24th April 2002.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: mortaliy 0/10
Mortality:
All animals survived until the end of the observation period of 14 days.
Clinical signs:
No signs of systemic toxicity were observed
Body weight:
A slight weight loss was recorded for 3 of 5 female animals during the first week, but all of the female animals showed weight gain during the second week. According to discussion by the study authors, the effects on weight development might be secondary to the dressing, and toxicological relevance of this finding cannot clearly be concluded. The male animals showed weight gain during the first and the second week of the observation.
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.
Other findings:
Signs of irritation:
- Erythema grade 1 was observed in 1 of 5 female animals. Eschar, desquamation and scratches were observed in 1 of 5 female animals.
- No signs of irritation were found for the male animals.
All signs of irritation were reversible within the observation period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) 1272/2008
Conclusions:
The LD50-value for acute dermal toxicity of MAPTAC is > 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study according to OECD guideline 402 (adopted 24th Feb, 1987), EU Method B.3 (adopted 30 May 2008), 5 male and 5 female young adult WISTAR Crl: WI(Han) rats were dermally exposed to MAPTAC for 24 hours under a semiocclusive dressing to approx. 10% of body surface area at doses of 2000 mg/kg bw (based on active ingredient). Animals then were observed for 14 days.

No animal died. Erythema grade 1 was observed in 1 of 5 female animals. Eschar, desquamation and scratches were observed in 1 of 5 female animals. No signs of irritation were found for the male animals. All signs of irritation were reversible within the observation period. No clinical signs of systemic toxicity were observed. Weight gain was positive and within normal range, except for 3 female rats which temporarily lost weight in the first week. No macroscopic substance related pathologic organ findings were noted during necropsy.

Dermal LD50

Males > 2000  mg/kg bw

Females > 2000  mg/kg bw

Combined > 2000  mg/kg bw

 

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Reliable (RL = 1 - 2), relevant and adequate data are available for the acute oral and dermal toxicity of MAPTAC.

 

Acute oral toxicity

In an acute oral toxicity study, groups of nonfasted male Wistar rats were given a single oral dose of MAPTAC (40% by weight in water) at doses of  5.0 and 10.0 mL/kg bw corresponding to 5300 and 10600 mg/kg bw, respectively based on a density of 1.06 g/cm³, and observed for 14 days. 3 animals in the lower dose group and 10 animals in the higher dose group were used.

No mortality occurred in the 5 mL/kg dose group; 1/10 died in the 10.0 mL/kg dose group. Sluggishness was observed in the higher dose group up to 6 hours after dosing, but all surviving animals had recovered on day 2. No abnormalities were observed at necropsy in the surviving animals.

Oral LD50 Males > 10600 mg/kg bw

The LD50 determined refers to the test substance as delivered by the sponsor. The amount of active ingredient in the test substance is 40%. Therefore the calculated oral LD50 referring to 100% active ingredient is > 4240 mg/kg bw.

 

Acute inhalative toxicity

A study on acute inhalation toxicity is unjustified in accordance to REACH regulation Annex VIII, column 2 due to exposure considerations as well as in accordance to REACH regulation Annex XI due to scientific considerations. The use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Furthermore, systemic toxicity relevant to humans did not appear in acute by oral or dermal exposure. Considering the exposure probability and the available information on the intrinsic toxic activity of the substance, an inhalative systemic toxicity risk to humans is unlikely and therefore, the conduct of an inhalative toxicity study is not scientifically necessary. Thus, also animal welfare is respected according to REACH intentions.

Acute dermal toxicity

In an acute dermal toxicity study according to OECD guideline 402 (adopted 24th Feb, 1987), EU Method B.3 (adopted 30 May 2008), 5 male and 5 female young adult WISTAR Crl: WI(Han) rats were dermally exposed to MAPTAC for 24 hours under a semiocclusive dressing to approx. 10% of body surface area at doses of 2000 mg/kg bw (based on active ingredient). Animals then were observed for 14 days.

No animal died. Erythema grade 1 was observed in 1 of 5 female animals. Eschar, desquamation and scratches were observed in 1 of 5 female animals. No signs of irritation were found for the male animals. All signs of irritation were reversible within the observation period. No clinical signs of systemic toxicity were observed. Weight gain was positive and within normal range, except for 3 female rats which temporarily lost weight in the first week. No macroscopic substance related pathologic organ findings were noted during necropsy.

Dermal LD50 Males > 2000 mg/kg bw

Dermal LD50 Females > 2000 mg/kg bw

Dermal LD50 Combined > 2000 mg/kg bw

 

This is supported by a further study: 

In an acute dermal toxicity study, groups of male Albino rabbits weredermally exposed to MAPTAC (40% by weight in water) for 24 hours at doses of 10 mL/kg bw corresponding to 10600 mg/kg bw (based on density of 1.06 g/cm³). Substance was applied to clipped, unabraded skin. Treated skin areas were covered, type of coverage not further specified. Animals then were observed for 14 days.

No animal died. No signs of irritation were found . No signs of systemic toxicity were observed. Weight gain was positive. No macroscopic substance related pathologic organ findings were noted during necropsy.

Dermal LD50 Males > 10600 mg/kg bw

The LD50 determined refers to the test substance as delivered by the sponsor. The amount of active ingredient in the test substance is 40%. Therefore the calculated oral LD50 referring to 100% active ingredient is > 4240 mg/kg bw.

 

Based on the available information, the acute toxicity of MAPTAC is low for oral and dermal routes of administration in rat.There are no data gaps in acute toxicity. Even though there is no information on acute inhalative toxicity, there is no reason to believe that the acute toxicity is higher for this route of exposure. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.


Justification for selection of acute toxicity – oral endpoint
pre-guideline study similar to OECD guideline, pre-GLP

Justification for selection of acute toxicity – inhalation endpoint
Inhalation is no relevant route of exposure and testing by inhalation is not appropriate. Exposure of humans via inhalation is unlikely taking into account the low vapour pressure and the low possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint
OECD guideline study, no deviations, GLP

Justification for classification or non-classification

Based on the available data, MAPTAC does not need to be classified for acute toxicity according to regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC. Thus, no labelling is required.