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Diss Factsheets

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
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: Guideline study without detailed documentation. Peer-reviewed database.
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
Males: 43 days (starting 14 days before mating)
Females: from 14 days before mating to day 3 of lactation (41 -52 days)
Frequency of treatment:
once daily
Remarks:
Doses / Concentrations:
0 (vehicle), 40, 200, 1000 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: As the LD50 value of > 2000 mg/kg was known, a preliminary test to decide the highest dose level at 30, 100, 300, and 1000 mg/kg/day for 14 days was conducted. At 1000 mg/kg/day, decrease of body weight in males and suppression of body weight increase in females were observed. Then the highest dose level for the test was set at 1000 mg/kg/day.
- Premating exposure period: 14 days
- Duration of test: 41 -52 days
- Post-exposure period: 1 day
The compound had no effects on reproductive parameteres such as the mating index, the fertility index, numbers of corpora Iutea or implantations, the implantation index, the delivery index, the gestation index, gestation length or parturition. Three dams of the 1000 mg/kg group, however, lost all their pups in the lactation period.
Significant adverse effects were observed in animals of the 1000 mg/kg/day group, especially in females. These adverse effects observed in females were as follows:
- 3 females out of 12 died.
- By the observation, late onset of twitching, chronic convulsion, suppression of body weight gain and a decrease in food consumption in lactation period were observed.
- By the histopathological examination, the degeneration of nerve fibers in the brain and the spinal cord, and the hyperplasia of the mucosa in gastric tract, the oedema and inflammatory ceII infiltration in the forestomach, and the atrophy of the thymus were revealed. Also the increases in the weight of the kidney and the adrenals without histopathological changes were observed.
Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: Effects on fertility and related parameters
On examination of neonates, the 1000 mg/kg dose was associated with a decrease in body weight and a low viability index. There were no significant differences in the number of offspring or live offspring, the sex ratio or the live birth index. No abnormalities ascribable to the compound were found for external features, clinical signs or necropsy findings for the offspring.
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
200 mg/kg bw/day
Sex:
male/female
Basis for effect level:
other: body weight of neonates and viability index
Reproductive effects observed:
not specified

Reproductive parameters:

 

Dose

(mg/kg)

0

40

200

1000

No. of pairs examined

12

12

12

10

No of pairs with successful mating

12

12

11

10

Mating index

(%)

100.0

100.0

91.7

100.0

No. of pregnant females

12

12

11

9

Fertility index

(%)

100.0

100.0

100.0

90.0

Pairing days until mating

(mean ± SD)

2.5 ± 1.0

3.1 ± 1.0

3.9 ± 3.0

2.8 ± 1.0

No. of estrous stages without mating

(mean ± SD)

0.0 ± 0.0

0.0 ± 0.0

0.1 ± 0.3

0.0 ± 0.0

 

Mating index (%) = (No. of pairs with successful mating / No. of pais examined) x 100

Fertility index (%) = (No. of prgnant animals / No. of pairs with successful mating) x 100

 

_

Developmental parameters:

 

Dose

(mg/kg)

0

40

200

1000

No. of females examined

12

12

11

8

Live birth index

(%)

98.03 ± 4.52

100.00 ± 0.00

93.18 ± 22.61

89.06 ± 12.64

No. of live pups on day 0

(mean)

14.3 +/-1.6

15.5 +/-1.2

15.5 +/-5.1

11.0 +/-3.7

No. of live pups on day 4

(mean)

14.0 +/-1.5

15.5 +/-1.2

14.0 +/-3.7

7.8 +/-4.2

Body weight of pups on day 0 (g)

Male (mean ± SD)

7.2 ± 0.4

6.6 ± 0.4

6.9 ± 0.7

6.4 ± 1.1*

Female (mean ± SD)

6.8 ± 0.6

6.3 ± 0.5

6.5 ± 0.7

6.0 ± 0.9*

Body weight of pups on day 4 (g)

Male (mean ± SD)

11.1 ± 1.1

10.4 ± 0.9

10.8 ± 2.0

10.2 ± 2.5

Female (mean ± SD)

10.7 ± 1.3

9.8 ± 1.0

10.4 ± 2.0

9.8 ± 1.8

 

* = Significantly different from control; p<0.05

Conclusions:
Under the conditions of this study, the NOAEL for the developmental toxicity is considered to be 200 mg/kg/day. A lower body weight gain and a lower viability index were observed in the pups from females of the 1000 mg/kg/day group. There were no adverse effecst on fertility related parameters even at 1000mg/kg/day, this could therfore be considered as a NOAEL for fertility although it was not a NOAEL for the parental females.
Executive summary:

The study was performed according to OECD TG 422 in compliance with GLP.

SD (Crj: CD) rats received gavage doses of 0 (vehicle; corn oil), 40, 200 and 1000 mg/kg/day, for males starting from 14 days before mating for 43 days and in females from 14 days before mating to day 3 of lactation. The female animals were sacrificed on day 4 of lactation.

There were no effects on the reproductive parameters such as the mating index, the fertility index, the number of corpora lutea or implantations, the implantation index, the delivery index, the gestation index and the gestation length or the parturition. Three females in the 1000 mg/kg/day group, however, lost all of their pups during the lactation period. Females in the 1000 mg/kg/day group showed the following adverse effects in the repeated oral dose test: death of 3 animals out of 12, late onset of twitching, chronic convulsion, the suppression of body weight gain, degeneration of nerve fibers in the brain and spinal cord, hyperplasia of the mucosa in die gastric tract, oedema and inflammatory cell infiltration in the forestomach, atrophy of the thymus, increase in the weight of the kidneys and the adrenals without histopathological changes.

The pups from the females in the 1000 mg/kg/day group showed lower body weights, and the viability index of the pups was decreased due to maternal nursery activity. By external inspection, no abnomalities were found.

Conclusion: Under the conditions of this study, the NOAEL for the reproductive/developmental toxicity is considered to be 200 mg/kg/day. However there were in fact no effects on fertlity at 1000mg/kg despite the severe toxicty seen in the parental females.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
There is no study investigating developmental toxicity for 2-tert-butylaminoethyl methacrylate but there is Klimisch 2 OECD 422 repeat dose, gavage oral dosing study with reproduction/developmental screening test in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. A NOAEL of 1000 mg/kg bodyweight/day was established, it is considered acceptable to use this value for read across to establish DNELs.
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Quality of whole database:
We do not have an inhalation test for reproduction toxicity, for 2-tert-butylaminoethyl methacrylate but there is a high quality OECD422 study via the oral (gavage) route for the read across substance 2-(dimethylamino)ethyl methacrylate. ECHA guidance allows the NOAEL from this study to be used to calculate the systemic inhalation DNEL, with an appropriate addition assessment factor of 2. The database is therefore considered to be adequate.
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Quality of whole database:
We do not have a dermal test for reproduction toxicity (fertility), but there is Klimisch 2 OECD422 repeat dose, gavage oral dosing study in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. ECHA guidance allows the NOAEL from this study to be used to calculate the systemic dermal DNEL, as dermal absorption is assumed to be the same as oral ingestion, which is probably conservative for both the read across substance 2-(dimethylamino)ethyl methacrylate and 2-tert-butylaminoethyl methacrylate. The database is therefore considered to be adequate.
Additional information

We do not have an inhalation study investigating possible effects on fertility for2-tert-butylaminoethyl methacrylate, but there is Klimisch 2 OECD422 repeat dose, gavage oral dosing study in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. This study is considered adequate to assess the potential for effects of fertility. Even at the highest dose of 1000 mg/kg bodyweight/day which was producing severe maternal toxicity, including the eventual death of three of the females, there were no effects on reproductive (fertility) parameters, such as mating index, the fertility index, numbers of corpora lutea or implantations. Therefore despite the severe toxic effects seen later in the study in the parental females at the 1000mg/kg bodyweight/day dose level, this dose level was in fact a NOAEL for effects on fertility related parameters.

Short description of key information:

We do not have an inhalation study investigating possible effects on fertility for 2-tert-butylaminoethyl  methacrylate, but there  is Klimisch 2 OECD422 repeat dose,  gavage oral dosing study in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2.  This study is capable of detecting effects on fertility and related parameters for the parental animals, as well as many aspects of developmental toxicity.

Justification for selection of Effect on fertility via oral route:

There is no study investigating the possible effects on fertility and related reproductive parameters for 2-tert-butylaminoethyl methacrylate but there  is Klimisch 2 OECD422 combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in the rat on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2.  It is a GLP study which has been reviewed by the Japanese government; there were severe toxic effects in the parental females at the 1000 mg/kg bodyweight /day top dose.  Even at this highest dose of 1000 mg/kg bodyweight/day which was producing severe maternal toxicity, including the eventual death of three of the females, there were no effects on reproductive (fertility) parameters, such as mating index, the fertility index, numbers of corpora lutea or implantations.  Therefore despite the severe toxic effects seen later in the study in the parental females at the 1000 mg/kg bodyweight/day dose level, this dose level was in fact a NOAEL for effects on fertility related parameters.

Justification for selection of Effect on fertility via inhalation route:

We do not have an inhalation study investigating possible effects on fertility for 2-tert-butylaminoethyl  methacrylate, but there  is Klimisch 2 OECD422 repeat dose,  gavage oral dosing study in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2.  Inhalation is not expected to be a significant route of exposure due to the containment required as any vapour generated would be irritant/corrosive.  Testing of corrosive substances by inhalation would be technically difficult as none corrosive exposure would have to be established.  The additional factor of 2 as recommended by ECHA, when using oral data to calculate an inhalation long term systemic DNEL, assumes 100% absorption by inhalation and 50% by the oral route.  Based on this, using the REACH guidance a DNEL for systemic effects from inhalation can be calculated for the oral NOAEL.  Therefore it is not scientifically justified to carry out an inhalation study; this avoids the use of additional animals.

Justification for selection of Effect on fertility via dermal route:

We do not have an inhalation study investigating possible effects on fertility for 2-tert-butylaminoethyl  methacrylate, but there  is Klimisch 2 OECD422 repeat dose,  gavage oral dosing study in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2.  Both substances are expected to be readily absorbed via the oral route.  ECHA guidance allows for the calculation of a systemic dermal DNEL based on the oral NOAEL , as the same absorption is assumed by the oral and dermal route,  it is likely that dermal absorption would be lower than oral so this is a conservative assumption.  Therefore it is not considered scientifically justified to perform an animal study by the dermal route.

Effects on developmental toxicity

Description of key information

We do not have a dermal study investigating possible effects on developmental toxicity  for 2-tert-butylaminoethyl  methacrylate, but there  is Klimisch 2 OECD422 combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2.  This study is a screening study, which is capable of detecting adverse effects on the pre and post implantation losses etc and survival and development of the offspring up to day 4 after parturition.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
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: Guideline study without detailed documentation. Peer-reviewed database.
Qualifier:
according to guideline
Guideline:
other: OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes
Species:
rat
Strain:
Crj: CD(SD)
Details on test animals or test system and environmental conditions:
- Sex: male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
Males: 43 days (starting 14 days before mating)
Females: from 14 days before mating to day 3 of lactation (41 -52 days)
Frequency of treatment:
once daily
Remarks:
Doses / Concentrations:
0 (vehicle), 40, 200, 1000 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
12
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: As the LD50 value of > 2000 mg/kg was known, a preliminary test to decide the highest dose level at 30, 100, 300, and 1000 mg/kg/day for 14 days was conducted. At 1000 mg/kg/day, decrease of body weight in males and suppression of body weight increase in females were observed. Then the highest dose level for the test was set at 1000 mg/kg/day.
- Premating exposure period: 14 days
- Duration of test: 41 -52 days
- Post-exposure period: 1 day
Details on maternal toxic effects:
Details on maternal toxic effects:
The compound had no effects on reproductive parameteres such as the mating index, the fertility index, numbers of corpora Iutea or implantations, the implantation index, the delivery index, the gestation index, gestation length or parturition.
Significant adverse effects were observed in animals of the 1000 mg/kg/day group, especially in females. These adverse effects observed in females were as follows:
- 3 females out of 12 died.
- By the observation, late onset of twitching, chronic convulsion, suppression of body weight gain and a decrease in food consumption in lactation period were observed.
- By the histopathological examination, the degeneration of nerve fibers in the brain and the spinal cord, and the hyperplasia of the mucosa in gastric tract, the oedema and inflammatory ceII infiltration in the forestomach, and the atrophy of the thymus were revealed. Also the increases in the weight of the kidney and the adrenals without histopathological changes were observed.
Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
mortality
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Details on embryotoxic / teratogenic effects:
On examination of neonates, the 1000 mg/kg dose was associated with a decrease in body weight and a low viability index. There were no significant differences in the number of offspring or live offspring, the sex ratio or the live birth index. All pups of three dams of the 1000 mg/kg group, died during the lactation period. No abnormalities ascribable to the compound were found for external features, clinical signs or necropsy findings for the offspring.
Key result
Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
fetal/pup body weight changes
changes in litter size and weights
changes in postnatal survival
Abnormalities:
not specified
Developmental effects observed:
not specified

Reproductive parameters:

 

Dose

(mg/kg)

0

40

200

1000

No. of pairs examined

12

12

12

10

No of pairs with successful mating

12

12

11

10

Mating index

(%)

100.0

100.0

91.7

100.0

No. of pregnant females

12

12

11

9

Fertility index

(%)

100.0

100.0

100.0

90.0

Pairing days until mating

(mean ± SD)

2.5 ± 1.0

3.1 ± 1.0

3.9 ± 3.0

2.8 ± 1.0

No. of estrous stages without mating

(mean ± SD)

0.0 ± 0.0

0.0 ± 0.0

0.1 ± 0.3

0.0 ± 0.0

 

Mating index (%) = (No. of pairs with successful mating / No. of pais examined) x 100

Fertility index (%) = (No. of prgnant animals / No. of pairs with successful mating) x 100

 

_

Developmental parameters:

 

Dose

(mg/kg)

0

40

200

1000

No. of females examined

12

12

11

8

Live birth index

(%)

98.03 ± 4.52

100.00 ± 0.00

93.18 ± 22.61

89.06 ± 12.64

No. of live pups on day 0

(mean)

14.3 +/-1.6

15.5 +/-1.2

13.1 +/-5.1

11.0 +/-3.7

No. of live pups on day 4

(mean)

14.0 +/-1.5

45.5 +/-1.2

14.0 +/-3.7

7.8 /-4.2

Body weight of pups on day 0 (g)

Male (mean ± SD)

7.2 ± 0.4

6.6 ± 0.4

6.9 ± 0.7

6.4 ± 1.1*

Female (mean ± SD)

6.8 ± 0.6

6.3 ± 0.5

6.5 ± 0.7

6.0 ± 0.9*

Body weight of pups on day 4 (g)

Male (mean ± SD)

11.1 ± 1.1

10.4 ± 0.9

10.8 ± 2.0

10.2 ± 2.5

Female (mean ± SD)

10.7 ± 1.3

9.8 ± 1.0

10.4 ± 2.0

9.8 ± 1.8

 

* = Significantly different from control; p<0.05

Conclusions:
Under the conditions of this study, the NOAEL for the reproductive/developmental toxicity is considered to be 200 mg/kg/day. A lower body weight gain and a lower viability index were observed in the pups from females of the 1000 mg/kg/day group.
Executive summary:

The study was performed according to OECD TG 422 in compliance with GLP.

SD (Crj: CD) rats received gavage doses of 0 (vehicle; corn oil), 40, 200 and 1000 mg/kg/day, for males starting from 14 days before mating for 43 days and in females from 14 days before mating to day 3 of lactation. The female animals were sacrificed on day 4 of lactation.

There were no effects on the reproductive parameters such as the mating index, the fertility index, the number of corpora lutea or implantations, the implantation index, the delivery index, the gestation index and the gestation length or the parturition. Three females in the 1000 mg/kg/day group, however, lost all of their pups during the lactation period. Females in the 1000 mg/kg/day group showed the following adverse effects in the repeated oral dose test: death of 3 animals out of 12, late onset of twitching, chronic convulsion, the suppression of body weight gain, degeneration of nerve fibers in the brain and spinal cord, hyperplasia of the mucosa in die gastric tract, oedema and inflammatory cell infiltration in the forestomach, atrophy of the thymus, increase in the weight of the kidneys and the adrenals without histopathological changes.

The pups from the females in the 1000 mg/kg/day group showed lower body weights, and the viability index of the pups was decreased due to maternal nursery activity. By external inspection, no abnomalities were found.

Conclusion: Under the conditions of this study, the NOAEL for the reproductive/developmental toxicity is considered to be 200 mg/kg/day.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
200 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
There is no study investigating developmental toxicity for 2-tert-butylaminoethyl methacrylate but there is Klimisch 2 OECD422 combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in the rat on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. The database is therefore considered to be adequate.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Quality of whole database:
We do not have an inhalation test for developmental toxicity, for 2-tert-butylaminoethyl methacrylate but there is an OECD422 combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in rats for the read across substance 2-(dimethylamino)ethyl methacrylate. ECHA guidance allows the NOAEL from this study to be used to calculate the systemic inhalation DNEL, with an appropriate addition assessment factor of 2. The database is therefore considered to be adequate.
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Quality of whole database:
We do not have a dermal test for developmental toxicity, but there is an OECD422 combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in rats for a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. ECHA guidance allows the NOAEL from this study to be used to calculate the systemic dermal DNEL, as dermal absorption is assumed to be the same as oral ingestion. The database is therefore considered to be adequate.
Additional information

There is no study investigating developmental toxicity for 2-tert-butylaminoethyl methacrylate but there is Klimisch 2 OECD422combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in the raton a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. It is a GLP study which has been reviewed by the Japanese government, there were severe toxic effects in the parental females at the 1000 mg/kg bodyweight /day top dose, three of the 12 died having lost their litters. There was a decrease in the viability at this dose level with none statistically significant reduction in the mean number of pups at day 0 and day 4 and statistically significant reduction in mean pup bodyweights at day 0 only. This reduced live birth index and viability can be strongly attributed to the severe maternal toxicity seen in the 1000 mg/kg dose parental females. There were no signs of any developmental abnormalities for external features, clinical signs or necropsy findings for the offspring. Due to the reduced pup survival the NOAEL for the offspring was considered to be 200 mg/kg bodyweight/day. But this was also the NOAEL for the parental females, supporting the view that these effects were due to severe maternal toxicity resulting in poor nurturing of the offspring.

Justification for selection of Effect on developmental toxicity: via oral route:

There is no study investigating developmental toxicity for 2-tert-butylaminoethyl methacrylate but there  is Klimisch 2 OECD422 combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in the rat on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2.  It is a GLP study which has been reviewed by the Japanese government, there were severe toxic effects in the parental females at the 1000 mg/kg bodyweight /day top dose, three of the 12 died having lost their litters.  There was a decrease in the viability at this dose level with none statistically significant reduction in the mean number of pups at day 0 and day 4 and statistically significant reduction in mean pup bodyweights at day 0 only.  This reduced live birth index and viability can be strongly attributed to the severe maternal toxicity seen in the 1000 mg/kg dose parental females. There were no signs of any developmental abnormalities for external features, clinical signs or necropsy findings for the offspring.  Due to the reduced pup survival the NOAEL for the offspring was considered to be 200 mg/kg bodyweight/day.  But this was also the NOAEL for the parental females, supporting the view that these effects were due to severe maternal toxicity resulting in poor nurturing of the offspring.  

Justification for selection of Effect on developmental toxicity: via inhalation route:

We do not have an inhalation study investigating possible effects on developmental toxicity  for 2-tert-butylaminoethyl  methacrylate, but there  is Klimisch 2 OECD422 combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2.  Inhalation is not expected to be a significant route of exposure due to the containment required as any vapour generated would be irritant/corrosive.  Testing of corrosive substances by inhalation would be technically difficult as none corrosive exposure would have to be established.  ECHA guidance allows for the calculation of a systemic inhalation DNEL based on the oral NOAEL, with appropriate assessment factors.  There is an adjustment by a factor of 2 to allow for expected higher absorption via inhalation compared to ingestion, which is probably conservative in this case.  Therefore it is not considered scientifically justified to perform an animal study by the inhalation route.

Justification for selection of Effect on developmental toxicity: via dermal route:

We do not have a dermal study investigating possible effects on developmental toxicity  for 2-tert-butylaminoethyl  methacrylate, but there  is Klimisch 2 OECD422 combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in rats on a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2.  ECHA guidance allows for the calculation of a systemic dermal DNEL based on the oral NOAEL , as the same absorption is assumed by the oral and dermal route,  it is likely that dermal absorption would be lower than oral so this is a conservative assumption.  Therefore it is not considered scientifically justified to perform an animal study by the dermal route.

Justification for classification or non-classification

There is no study investigating developmental toxicity for 2-tert-butylaminoethyl methacrylate but there is Klimisch 2 OECD422combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in the raton a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2. This study is considered adequate to assess the potential for effects of fertility. Even at the highest dose of 1000 mg/kg bodyweight/day which was producing severe maternal toxicity, including the eventual death of three of the females, there were no effects on reproductive (fertility) parameters, such as mating index, the fertility index, numbers of corpora lutea or implantations. There was a decrease in the viability at the 1000 mg/kg bodyweight/day dose level with none statistically significant reduction in the mean number of pups at day 0 and day 4 and statistically significant reduction in mean pup bodyweights at day 0 only. This reduced live birth index and viability can be strongly attributed to the severe maternal toxicity seen in the 1000 mg/kg dose parental females. There were no signs of any developmental abnormalities for external features, clinical signs or necropsy findings for the offspring.

There were no findings in the OECD 442 combined repeat dose oral (gavage) toxicity study with reproduction/developmental screening test in the raton a read across substance 2-(dimethylamino)ethyl methacrylate CAS No 2867-47-2 that require the classification of 2-tert-butyaminoethyl methacrylate for adverse effects on fertility and related parameters or for the developmental toxicity in the offspring based on the EU CLP(GHS) criteria.

Additional information