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Toxicological information

Toxicity to reproduction

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Administrative data

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: see 'Remark'
Remarks:
Based on metabolism models generated with OASIS TIMES, benzylamines metabolites are formed from the substance 2,6-Di-tert-butyl-alpha-(dimethylamino)-p-cresol (CAS 88-27-7). The substance CAS No. 1477-55-0 presents the functional group benzylamine. Therefore, the results obtained with the substance CAS No. 1477-55-0 can be used for the read-across approach.

Data source

Reference
Reference Type:
other: read-across
Title:
Unnamed
Year:
2012

Materials and methods

Principles of method if other than guideline:
Read-across from experimental data on an analogue.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Molecular formula (if other than submission substance): C8H12N2
- Molecular weight (if other than submission substance): 136.2
- Smiles notation (if other than submission substance): c1c(cccc1CN)CN
- InChl (if other than submission substance): InChI=1S/C8H12N2/c9-5-7-2-1-3-8(4-7)6-10/h1-4H,5-6,9-10H2
- Structural formula attached as image file (if other than submission substance): see Fig.

Results and discussion

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
870 mg/kg bw/day

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Based on metabolism models generated with OASIS TIMES, benzylamines metabolites are formed from the substance 2,6-Di-tert-butyl-alpha-(dimethylamino)-p-cresol (CAS 88-27-7).The substance CAS No. 1477-55-0 presents the functional group benzylamine. Therefore, the results obtained with the substance CAS No. 1477-55-0 can be used for the read-across approach.

 

As indicated in the European Chemical Agency Practical Guide 6 “How to report read –across and categories”, the structural grouping was realized using “OECD QSAR APPLICATION TOOL BOX” (see attachment).

 

Table 1: Data Matrix, Analogue Approach

CAS Number

 

1477-55-0

88-27-7

CHEMICAL NAME

 

Analogue

1,3-bis(aminomethyl)benzene

 

Target chemical

2,6-di-tert-butyl-4-[(dimethylamino)methyl]phenol

PHYSICO-CHEMICAL DATA

Melting Point

Experimental results:

No data

 

Experimental results:

Handbook: 94 ºC

Boiling Point

Experimental results:

247 ºC

Weight of evidence:

Handbook: 179 ºC (40 mm Hg)

Estimated data: Boiling point EPISUITE = 336.78 ºC (Adapted Stein & Brown method) (MPBPWIN v1.43)

Density

No data

Experimental results:

1.023 at 20 ºC

 

Vapour Pressure

Estimated data:

0.0146 mm Hg at 25 ºC

Estimated data:

Vapour pressure EPISUITE = 1.69E-005 mm Hg at 25 ºC (Modified Grain method) (MPBPWIN v1.43)

0.00226 Pa at 25 ºC (Modified Grain method) (MPBPWIN v1.43)

Partition Coefficient (log Kow)

Estimated data:

0.15

 

 

Estimated data:

The calculated partition coefficient is 4.24

(EPI Suite, KOWWIN v1.68 estimate).

 

Water solubility

 

Estimated data:

6.64E+005 mg/L at 25 ºC

 

Experimental results:

10.7 mg/L at 20 ºC (pH 9.2)

 

ENVIRONMENTAL FATE and PATHWAY

Aerobic Biodegradation

 

Estimated data:

No readily biodegradable

(BIOWIN v4.10)

 

Estimated data:

No readily biodegradable

(BIOWIN v4.10)

 

Anaerobic Biodegradation

No data

 

No data

ENVIRONMENTAL TOXICITY

Acute Toxicity to Fish

Key study: Estimated data:

96-h LC50 for fish is 312.233 mg/l (ECOSAR v1.00a, aliphatic amines class).

96-h LC50 for fish is 464.593 mg/l (ECOSAR v1.00a, benzyl amines class).

Key study: Estimated data:

96-h LC50 for fish is 1.346 mg/l

(ECOSAR v1.00a, phenol amines class).

96-h LC50 for fish is 2.092 mg/l

(ECOSAR v1.00a, aliphatic amines class).

96-h LC50 for fish is 0.907 mg/l

(ECOSAR v1.00a, phenols class).

Acute Toxicity to Aquatic Invertebrates

 

Key study: Estimated data:

48-h LC50 for Daphnia is 21.47 mg/l (ECOSAR v1.00a, aliphatic amines class)

 

Key study: Estimated data:

48-h LC50 for Daphnia is 0.659 mg/l

(ECOSAR v1.00a, phenol amines class)

48-h LC50 for Daphnia is 0.335 mg/l

(ECOSAR v1.00a, aliphatic amines class)

48-h LC50 for Daphnia is 0.746 mg/l

(ECOSAR v1.00a, phenols class)

Toxicity to Aquatic Plants

 

Key study: Estimated data:

96-h EC50 for green algae is 5.044 mg/l (ECOSAR v1.00a, aliphatic amines class).

 

Key study: Estimated data:

96-h EC50 for green algae is 0.644 mg/l

(ECOSAR v1.00a, phenol amines class).

96-h EC50 for green algae is 0.297 mg/l

(ECOSAR v1.00a, aliphatic amines class).

96-h EC50 for green algae is 2.760 mg/l

(ECOSAR v1.00a, phenols class).

MAMMALIAN TOXICITY

Acute Oral

 

No data

 

 

Experimental results:

LD50 = 461 mg/kg

 

Acute Inhalation

No data

 

No data

Acute Dermal

No data

 

Experimental results:

LD50 > 4000 mg/kg

 

Skin irritation / Eye irritation

No data

 

Experimental results:

Not a skin irritant.

Eye irritant.

 

Skin sensitisation

No data

Experimental results:

Skin sensitiser

 

Repeated Dose

Repeated dose toxicity: oral:

Key study: 28-day study in rats:

NOEL 150 mg/kg/day

 

Read-across:

NOEL 290 mg/kg bw/day

 

Genetic Toxicity in vitro

 

Gene mutation in bacteria

 

Key study:

Negative

Read-across:

Negative

 

Chromosomal aberration

 

Key study: 

Negative

 

Read-across:

Negative

 

Mammalian gene mutation

 

Key study: 

Negative

 

Read-across:

Negative

 

Genetic Toxicity in vivo

 

No data

No data

Carcinogenicity

 

No data

No data

Reproductive Toxicity:

developmental toxicity

Key study: Experimental results:

Screening for reproduction toxicity:

Test chemical administration had no influence on mating ability, fertility, duration of oestrus or duration of pregnancy and parturition.

 

NOAEL for reproductive/developmental toxicity (F1 offspring) = 450 mg/kg bw/day.

Read-across:

NOAEL for reproductive/developmental toxicity

(F1 offspring) = 870 mg/kg bw/day.

 

Applicant's summary and conclusion

Conclusions:
No adverse effects were observed in terms of copulation, fertility, delivery and nursing of parents, and the viability, body weight and morphology of offsprings.

Based on experimental data, the read-across approach is applied and the NOAEL for reproductive/developmental toxicity (F1 offspring) was 870 mg/kg b.w./day.
Executive summary:

Based on metabolism models generated with OASIS TIMES, benzylamines metabolites are formed from the substance 2,6-Di-tert-butyl-alpha-(dimethylamino)-p-cresol (CAS 88-27-7).The substance CAS No. 1477-55-0 presents the functional group benzylamine. Therefore, the results obtained with the substance CAS No. 1477-55-0 can be used for the read-across approach.

No adverse effects were observed in terms of copulation, fertility, delivery and nursing of parents, and the viability, body weight and

morphology of offsprings.

NOAEL for reproductive/developmental toxicity (F1 offspring) was 870 mg/kg b.w./day.