Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: oral
Adequacy of study:
other information

Data source

Reference
Title:
"Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test of 2-(Dimethylamino)ethyl acrylate|by Oral Administration in Rats"
Author:
Ministry of Health and Welfare, Japan
Year:
1997
Bibliographic source:
Toxicity Testing Reports of Environmental Chemicals, vol.5, 583-594

Materials and methods

Principles of method if other than guideline:
Method: other: OECD combined repeat dose and reproductive/developmental toxicity screening test
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Automatically generated during migration to IUCLID 6, no data available
IUPAC Name:
Automatically generated during migration to IUCLID 6, no data available
Details on test material:
IUCLID4 Test substance: other TS: 99.9 wt% purity, NIPPON SHOKUBAI CO.,LTD. Lot No. 5P07

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
males; 43 day
females; from 14 day before mating to day 3 of lactation
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0 (vehicle), 4, 20, 100 mg/kg/day
Basis:

Control animals:
other: yes, corn oil
Details on study design:
Post-exposure period: 1 day

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
20 mg/kg bw/day (nominal)
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

RS-Freetext:
The NOAELs for repeat dose toxicity are considered to be 20
mg/kg/day for both sexes. 
- Male:
  At 100 mg/kg/day, no death was occured.
  - By the observation, transient suppression of body weight gain and  decrease in food consumption were observed.
  - By the necroscopy findings, thickening of the wall of
the forestomach and enlargement of the pancreatico-duodenal
lymph nodes were observed. 
  - By the histopathological examination:
   Ulceration, inflammatory cell infiltration and
hyperplasia of the mucosa in the forestomach, and hyperplasia of plasma  cells in the pancreatioco-duodenal lymph nodes were revealed. 
  - By the hematological and blood chemical examination:
   A increase in reticulocyte, platelet and segmented
neutrophil counts, a decrease in differential lymphocytes counts and  albumin were revealed.
  At 20 mg/kg/day, similar histopathological changes were
observed in the forestomach. 
  At 4 mg/kg/day, no effects were observed.
Remark:
Thus the NOEL for males was considered as 4 mg/kg/day. 
However, Histopathological changes In forestomach were based on  stimulative of 2-(dimethylamino)ethyl acrylate.  Then the NOAEL for males  was considered as 20 mg/kg/day.

- Female:
  At 100 mg/kg/day, 2 females out of 12 died.
  - By the observation, a decrease in the absolute thymus
weight was observed.
  - By the necroscopy examination, similar changes as males
were observed.
  - By the histopathological examination, similar changes as males were  observed.
  At 20 mg/kg/day and 4 mg/kg/day, no effects were observed.

The result of the hematological and blood chemical
examination in male rats are summarized below.

Dose [mg/kg/day]             0     4    20  100
---------------------------  ---- ---- ---- -----
No. of animals                12   12   12   12
Reticulo (%)                  25   27   26   30**
Plt [10E4/ul]                103  103  105  115*
Differential
lymphocytes counts (%)        81   84   82   68**
Differential segmented
neutrophils counts [10E2/ul]  16   12   15   39**
Albumin [g/dl]                3.7  3.8  3.7  3.6*
-------------------------------------------------

significantly different from control: *=p<0.05,**=p<0.01

The major histopathological findings in rats are summarized
below.

Male:
Dose [mg/kg/day]           Note   0  4  20  100
-------------------------  ---- --- --- --- ----
No. of animals                   12 12  12   12
Findings in Lymph node
(pancreatico-duodenal)
 -Hyperplasia, plasma cell  +     #  #   #   7/7
Finding in forestomach
-Hyperplasia, mucosa        +     0  0   2   12**
-Inflam. cell infiltration  +     0  0   1    0 
                            ++    0  0   1   11**
 -Ulcer                     +     0  0   0    0  
                            ++    0  0   1   11**
-------------------------------------------------
 Note: +  slight
       ++ moderate
        # not examined
Female:
Dose [mg/kg/day]           Note  0  4  20 100 100 
                                            (dead)
------------------------   ---- -- --- -- --- ----
No. of animals                  12 12  12  10   2
Findings in Lymph node
 (pancreatico-duodenal)                        
-Hyperplasia, plasma cell   +    #  #   #  7/7  #
Finding in forestomach             
-Hyperplasia, mucosa        ++   0  0   0 10**  1 
-Inflam. cell inifilt       ++   0  0   0 10**  1 
-Ulcer                      ++   0  0   0 9**   1
--------------------------------------------------

Applicant's summary and conclusion

Conclusions:
CL-Freetext:
The NOAEL is considered to be 20 mg/kg/day for both sexes.