Octyl (R)-2-(4-chloro-2-methylphenoxy)propionate

Immunotoxicity

Administrative data

Endpoint:

immunotoxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: published data, documentation insufficient for assessment

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Pathomorphologische und hämatologische Untersuchungen zur Immuntoxizität der Phenoxyalkansäure Mecoprop an Ratten

Author:

Moeller T & Solecki R

Year:

1989

Bibliographic source:

Zeitschrift für die gesamte Hygiene und ihre Grenzgebiete 35 (5), 258-260

Reference 2

Reference Type:

secondary source

Title:

No information

Author:

The Danish Environmental Protection Agency

Year:

1998

Bibliographic source:

Mecoprop-P, EU Review Programme on active substances in Plant Protection Products, Scientific Evaluation and Assessment, Draft December 1998 (Volume 3, Annex B, ) and Addendum II July 2002; see also SANCO/3065/99-Final, 2003

Materials and methods

Administration / exposure

Details on study design:

Cited from Mecoprop-P, EU Review Programme on active substances in Plant Protection Products, Scientific Evaluation and Assessment, The Danish Environmental Protection Agency, Draft December 1998 (Volume 3, Annex B) and Addendum II July 2002:
"An acute, a 14 day and a 90 day oral study was conducted with Wistar rats..." For dose levels and no. of rats per group see table below.
"The animals were dosed by gavage. Racemic mecoprop (potassium salt, purity of 97%) was dissolved in water and the animals were dosed with a volume of 5 ml/kg bw.
Organ weights of thymus and spleen were determined. Histopathology was performed on thymus, spleen and mesenteric lymph nodes. The spleen was subjected to morphometry. Total and differential leucocyte counts were performed. Housing conditions only differed marginally from the conditions described in OECD 401, OECD 407 and 408.
From the reporting of the studies it can not be seen, if the studies were conducted according to any guidelines or GLP.
No information about body weight gain, organ weights of other organs (liver, kidney) etc. is available and some details on e.g. blood chemistry are lacking. Therefore the report can only be used as supplementary to the other tests."

Results and discussion

Results of examinations

Details on results:

Cited from Mecoprop-P, EU Review Programme on active substances in Plant Protection Products, Scientific Evaluation and Assessment, The Danish Environmental Protection Agency, Draft December 1998 (Volume 3, Annex B) and Addendum II July 2002:
"Results:
Thymus. The thymus weight was significantly (p<0.05, t-test) decreased at 1300 mg/kg bw in the acute study, at 320 and 800 mg/kg bw in the 14-day study and at 8 mg/kg bw (males), 80 mg/ kg bw (males) and 320 mg/ kg bw (males + females) in the 90-day study. At the histological examination degenerative processes at and above 320 mg/kg bw/day were observed consisting of decreased density of lymphocytes and increased decay of leucocytes in the cortex of the organ. No significant findings were noted in the medulla.
Spleen. The organ weight was significantly reduced at 1300 mg/kg bw in the acute study and at 800 mg/kg bw in the 14-day study. At microscopy a reduction in white pulp tissue was noted in all of the studies, and in the 14-day and 90-day study at the same time enlargement of the haematopoietic tissue of the spleen was found. These findings were confirmed by morphometric examination of the spleen tissue from the animals in the 14-day study, where the changes occurred to a significant extent at 320 mg/kg bw.
No histological changes were found in the mesenteric lymph nodes.
The number of total leucocytes was not affected. However, in the 14-day and the 90-day study significant dose-dependent changes in differential leucocyte counts were noted (decrease in lymphocytes and increase in neutrophilic granulocytes).
The results from these studies were interpreted as well known immunotoxic signs of increased glucocorticoid response. A stress symptom with increased adrenal secretion of glucocorticoids was suggested.
Discussion and conclusion:
The consistent findings between the three experiments, strongly indicates mecoprop exposure to affect thymus and spleen function and cause haematological changes. The reporting of the haematological effects do not allow for establishing a NOAEL, but the description of these findings are very brief. With respect to decrease in thymus organ weight NOAEL in the 90-day study is 0.8 mg/kg bw/day for male rats and 80 mg/kg bw/day for females."